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Original Articles
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PSMA expression in hepatic colorectal cancer metastasis
Eundong Park, Michel Kmeid, Xin Wang, Haiyan Qiu, Clifton G. Fulmer, Marcello P. Toscano, Nusret Bekir Subasi, Maciej Gracz, Hwajeong Lee
J Pathol Transl Med. 2026;60(1):107-123.   Published online January 14, 2026
DOI: https://doi.org/10.4132/jptm.2025.10.20
  • 358 View
  • 32 Download
AbstractAbstract PDFSupplementary Material
Background
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of various malignancies, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, PSMA expression in hepatic CRC metastasis has not been studied in detail. Methods: The PSMA expression in primary CRC and corresponding hepatic metastasis was evaluated by immunohistochemistry in a metastatic CRC cohort (n = 56), which was divided into subgroups according to treatment history and timing of metastasis. Demographic and histological characteristics of primary CRC were collected and their relationships with PSMA expression were examined. Additionally, the PSMA expression in resected HCC (n = 76) was compared with that of hepatic CRC metastasis. Results: In primary CRC, PSMA level showed a positive association with tumor size. Lower PSMA expression in hepatic metastasis was associated with higher primary CRC grade, advanced pTNM stage at the time of CRC resection, presence of tumor deposit, and unresectability of metastatic lesion. PSMA expression in primary CRC correlated with that in hepatic metastasis only in concurrent and untreated metastasis subgroup. PSMA expression in primary CRC and hepatic metastasis, regardless of treatment history and timing of metastasis, was not significantly different from that of HCC. Conclusions: Several adverse pathological features of primary CRC were associated with a lower PSMA expression in hepatic metastasis. PSMA expression in hepatic metastasis correlated with that of primary CRC only in concurrent and untreated subgroup. Primary HCC and hepatic CRC metastasis show comparable levels of PSMA expression.
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The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae Lee, Hye Eun Park, Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Gyeong Hoon Kang
J Pathol Transl Med. 2025;59(1):50-59.   Published online October 24, 2024
DOI: https://doi.org/10.4132/jptm.2024.09.26
  • 3,605 View
  • 279 Download
AbstractAbstract PDFSupplementary Material
Background
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
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Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation
Jun Sang Shin, Tae-Gyu Kim, Young Hwa Kim, So Yeong Eom, So Hyun Park, Dong Hyun Lee, Tae Jun Park, Soon Sang Park, Jang-Hee Kim
J Pathol Transl Med. 2023;57(6):305-314.   Published online November 7, 2023
DOI: https://doi.org/10.4132/jptm.2023.10.09
  • 6,924 View
  • 315 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary Material
Background
Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.
Methods
Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.
Results
Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.
Conclusions
Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

Citations

Citations to this article as recorded by  
  • Senescence, Aging and Disease Throughout the Gastrointestinal System
    Sofia Ferreira-Gonzalez, Tomonori Matsumoto, Eiji Hara, Stuart J. Forbes
    Gastroenterology.2025; 169(7): 1357.     CrossRef
  • Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants
    Muhammad Tufail, Yu-Qi Huang, Jia-Ju Hu, Jie Liang, Cai-Yun He, Wen-Dong Wan, Can-Hua Jiang, Hong Wu, Ning Li
    Aging and disease.2024;[Epub]     CrossRef
  • Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE)
    Eun Sol Chang, Kyoung Song, Ji-Young Song, Minjung Sung, Mi-Sook Lee, Jung Han Oh, Ji-Yeon Kim, Yeon Hee Park, Kyungsoo Jung, Yoon-La Choi
    Cancer & Metabolism.2024;[Epub]     CrossRef
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Prognostic and clinicopathological significance of Fusobacterium nucleatum in colorectal cancer: a systemic review and meta-analysis
Younghoon Kim, Nam Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2022;56(3):144-151.   Published online May 15, 2022
DOI: https://doi.org/10.4132/jptm.2022.03.13
  • 8,645 View
  • 144 Download
  • 12 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary Material
Background
Fusobacterium nucleatum has been identified to promote tumor progression in colorectal cancer (CRC). However, association between F. nucleatum and prognostic or clinicopathological features has been diverse among studies, which could be affected by type of biospecimen (formalin-fixed paraffin-embedded or fresh frozen [FF]).
Methods
Articles were systemically reviewed for studies that included the correlation between F. nucleatum and prognosis or clinicopathological features in CRC.
Results
Ten articles, eight studies with survival-related features involving 3,199 patients and nine studies with clinical features involving 2,655 patients, were eligible for the meta-analysis. Overall survival, disease-free survival, and cancer-specific survival were all associated with worse prognosis in F. nucleatum–high patients (p<.05). In subgroup analysis, only studies with FF tissues retained prognostic significance with F. nucleatum. In meta-analysis of clinicopathological variables, F. nucleatum level was associated with location within colon, pT category, MLH1 hypermethylation, microsatellite instability status, and BRAF mutation regardless of type of biospecimen. However, lymph node metastasis and KRAS mutation was only associated with F. nucleatum level in FF-based studies.
Conclusions
In conclusion, type of biospecimen could affect the role of F. nucleatum as a biomarker associated with clinicopathological features and prognosis.

Citations

Citations to this article as recorded by  
  • Unraveling the Role of Fusobacterium nucleatum in Colorectal Cancer: Molecular Mechanisms and Pathogenic Insights
    Linda Galasso, Fabrizio Termite, Irene Mignini, Giorgio Esposto, Raffaele Borriello, Federica Vitale, Alberto Nicoletti, Mattia Paratore, Maria Elena Ainora, Antonio Gasbarrini, Maria Assunta Zocco
    Cancers.2025; 17(3): 368.     CrossRef
  • Intratumoural pks Escherichia coli is associated with risk of metachronous colorectal cancer and adenoma development in people with Lynch syndrome
    Yen Lin Chu, Peter Georgeson, Mark Clendenning, Khalid Mahmood, Romy Walker, Julia Como, Sharelle Joseland, Susan G. Preston, Toni Rice, Brigid M. Lynch, Roger L. Milne, Melissa C. Southey, Graham G. Giles, Amanda I. Phipps, John L. Hopper, Aung K. Win, C
    eBioMedicine.2025; 114: 105661.     CrossRef
  • Fusobacterium nucleatum Enrichment in Colorectal Tumor Tissue: Associations With Tumor Characteristics and Survival Outcomes
    Amanda I. Phipps, Courtney M. Hill, Genevieve Lin, Rachel C. Malen, Adriana M. Reedy, Orsalem Kahsai, Hamza Ammar, Keith Curtis, Ningxin Ma, Timothy W. Randolph, Jing Ma, Shuji Ogino, Polly A. Newcomb, Meredith AJ. Hullar
    Gastro Hep Advances.2025; 4(6): 100644.     CrossRef
  • Enhancing fibroblast–epithelial cell communications: Serpine2 as a key molecule in Fusobacterium nucleatum–promoted colon cancer
    Xueke Li, Simin Luo, Yifang Jiang, Qiong Ma, Fengming You, Qixuan Kuang, Xi Fu, Chuan Zheng
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • The presence and relative abundance of salivary Fusobacterium nucleatum are not associated with colorectal cancer: a systematic review and meta-analysis
    Ellay Gutmacher, Bálint Zsombor Sárai, Petrana Martineková, Szilvia Kiss-Dala, Gergely Agócs, Péter Hegyi, Andrea Bródy, Ákos Zsembery
    Scientific Reports.2025;[Epub]     CrossRef
  • The role of oral microbiota in digestive system diseases: current advances and perspectives
    Yaqi Li, Yiping Xin, Wenlu Zong, Xiaoyu Li
    Journal of Oral Microbiology.2025;[Epub]     CrossRef
  • Fusobacterium Nucleatum in Colorectal Cancer: Relationship Among Immune Modulation, Potential Biomarkers and Therapeutic Implications
    Dalila Incognito, Giuliana Ciappina, Claudia Gelsomino, Antonio Picone, Pierluigi Consolo, Alessandra Scano, Tindara Franchina, Nicola Maurea, Vincenzo Quagliariello, Salvatore Berretta, Alessandro Ottaiano, Massimiliano Berretta
    International Journal of Molecular Sciences.2025; 26(19): 9710.     CrossRef
  • Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer
    Jihoon E. Joo, Yen Lin Chu, Peter Georgeson, Romy Walker, Khalid Mahmood, Mark Clendenning, Aaron L. Meyers, Julia Como, Sharelle Joseland, Susan G. Preston, Natalie Diepenhorst, Julie Toner, Danielle J. Ingle, Norelle L. Sherry, Andrew Metz, Brigid M. Ly
    British Journal of Cancer.2024; 130(5): 728.     CrossRef
  • The role of Fusobacterium nucleatum in cancer and its implications for clinical applications
    Wanyi Luo, Juxi Han, Xian Peng, Xuedong Zhou, Tao Gong, Xin Zheng
    Molecular Oral Microbiology.2024; 39(6): 417.     CrossRef
  • Fusobacterium nucleatum Load Correlates with KRAS Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma
    Koki Takeda, Minoru Koi, Yoshiki Okita, Sija Sajibu, Temitope O. Keku, John M. Carethers
    Cancer Research Communications.2023; 3(9): 1940.     CrossRef
  • Tumour Colonisation of Parvimonas micra Is Associated with Decreased Survival in Colorectal Cancer Patients
    Thyra Löwenmark, Anna Löfgren-Burström, Carl Zingmark, Ingrid Ljuslinder, Michael Dahlberg, Sofia Edin, Richard Palmqvist
    Cancers.2022; 14(23): 5937.     CrossRef
Case Study
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Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice
Evi Abada, Ifeoma C. Anaya, Othuke Abada, Anthony Lebbos, Rafic Beydoun
J Pathol Transl Med. 2022;56(2):97-102.   Published online January 21, 2022
DOI: https://doi.org/10.4132/jptm.2021.10.28
  • 8,165 View
  • 207 Download
  • 11 Web of Science
  • 9 Crossref
AbstractAbstract PDF
Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

Citations

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  • Exploring the Multifunctional Role of Alpha-Fetoprotein in Cancer Progression: Implications for Targeted Therapy in Hepatocellular Carcinoma and Beyond
    Hyunjung Kim, Minji Jang, Eunmi Kim
    International Journal of Molecular Sciences.2025; 26(10): 4863.     CrossRef
  • Rectal adenocarcinoma with a yolk sac tumor component: A rare case report and review of the literature
    Sato Nishida, Tomohiro Takeda, Tatsuya Shonaka, Shoichiro Mizukami, Masahide Otani, Mizuho Ohara, Chikayoshi Tani, Kimiharu Hasegawa, Yuki Kamikokura, Mishie Tanino, Hideki Yokoo
    International Cancer Conference Journal.2025;[Epub]     CrossRef
  • SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms
    Tairan Wang, Yan Jin, Mengyao Wang, Boya Chen, Jinyu Sun, Jiaying Zhang, Hui Yang, Xinyao Deng, Xingyue Cao, Lidong Wang, Yuanyuan Tang
    Molecular Medicine.2024;[Epub]     CrossRef
  • Gastric adenocarcinoma with enteroblastic differentiation in a 67-year-old man in Korea: a case report
    Hae Rin Lee, Gwang Ha Kim, Dong Chan Joo, Moon Won Lee, Bong Eun Lee, Kyung Bin Kim
    The Ewha Medical Journal.2024;[Epub]     CrossRef
  • Colorectal adenocarcinoma with clear cell changes: immunohistological and molecular findings in three cases
    Andreas Gocht, Carsten Heidel, Jutta Kirfel, Rita Vesce, Pamela Lazar-Karsten, Helen Pasternack, Madelaine Melzer, Phillip Hildebrand, Nicole Warkentin, Hendrik Schimmelpenning, Verena-Wilbeth Sailer
    Virchows Archiv.2024; 485(3): 569.     CrossRef
  • Ureteral Metastasis of Colonic Adenocarcinoma with Enteroblastic Differentiation: A Rare Case to be Distinguished from Clear Cell Adenocarcinoma of the Urinary Tract
    Hiroshi Minato, Akane Yoshikawa, Sho Tsuyama, Kazuyoshi Katayanagi, Kengo Hayashi, Yusuke Sakimura, Hiroyuki Bando, Tomohiro Hori, Yosuke Kito
    International Journal of Surgical Pathology.2023; 31(8): 1553.     CrossRef
  • Beyond liver cancer, more application scenarios for alpha-fetoprotein in clinical practice
    Chenyu Ma, Yuexinzi Jin, Yuhan Wang, Huaguo Xu, Jiexin Zhang
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • AIEgens assisted label free DNA supersandwich immunoassay for ultrasensitive α-fetoprotein detection
    Xiaowen Ou, Jingman Dai, Yiting Huang, Xiaoqin Xiong, Zhi Zheng, Xiaoding Lou, Fan Xia
    Giant.2022; 11: 100110.     CrossRef
  • Rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features arising in a patient with ulcerative colitis: a case report
    Takako Kihara, Ryuichi Kuwahara, Kurando Kusunoki, Tomohiro Minagawa, Yuki Horio, Motoi Uchino, Hiroki Ikeuchi, Seiichi Hirota
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Original Articles
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Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer
Hyunseung Oh, Soon Gu Kim, Sung Uk Bae, Sang Jun Byun, Shin Kim, Jae-Ho Lee, Ilseon Hwang, Sun Young Kwon, Hye Won Lee
J Pathol Transl Med. 2022;56(1):40-47.   Published online November 16, 2021
DOI: https://doi.org/10.4132/jptm.2021.10.07
  • 5,653 View
  • 163 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary Material
Background
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Citations

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  • Polo-like kinase 4 (PLK4) as a therapeutic target in breast cancer
    Armen Parsyan, Harjot Athwal, Vasudeva Bhat, Alison L Allan
    Carcinogenesis.2025;[Epub]     CrossRef
  • Polo-like kinase 4: A molecular linchpin in cancer and its management
    Durdana Muntaqua, Gagan Chhabra, Karla B. Anaya Aldrete, Nihal Ahmad
    iScience.2025; 28(12): 114186.     CrossRef
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MicroRNA-552 expression in colorectal cancer and its clinicopathological significance
Joon Im, Soo Kyung Nam, Hye Seung Lee
J Pathol Transl Med. 2021;55(2):125-131.   Published online February 19, 2021
DOI: https://doi.org/10.4132/jptm.2021.01.17
  • 5,583 View
  • 128 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary Material
Background
MicroRNA-552 (miR-552) has been reported to correlate with the development and progression of various cancers, including colorectal cancer (CRC). This study aimed to investigate miR-552 expression in cancer tissue samples compared to normal mucosal tissue and its role as a diagnostic or prognostic marker in CRC patients.
Methods
Normal mucosal tissues and primary cancer tissues from 80 surgically resected CRC specimens were used. Quantitative real-time polymerase chain reaction was performed for miR-552 and U6 small nuclear RNA to analyze miR-552 expression and its clinicopathological significance. Immunohistochemistry for p53 and phosphatase and tension homolog (PTEN) was performed to evaluate their association with miR-552 expression.
Results
miR-552 expression was significantly higher in primary cancer tissues compared to normal mucosal tissues (p<.001). The expression level of miR552 was inversely correlated with that of PTEN (p=.068) and p53 (p=.004). Survival analysis showed that high miR-552 expression was associated with worse prognosis but this was not statistically significant (p=.255). However, patients with CRC having high miR-552 expression and loss of PTEN expression had significantly worse prognosis than others (p=.029).
Conclusions
Our results suggest that high miR-552 expression might be a potential diagnostic biomarker for CRC, and its combined analysis with PTEN expression can possibly be used as a prognostic marker.

Citations

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  • MicroRNAs involved in colorectal cancer, a rapid mini-systematic review
    Sogol Shirzad, Majid Eterafi, Zeinab Karimi, Mahdi Barazesh
    BMC Cancer.2025;[Epub]     CrossRef
  • Diagnostic and Therapeutic Potential of Selected microRNAs in Colorectal Cancer: A Literature Review
    Grzegorz Sychowski, Hanna Romanowicz, Wojciech Ciesielski, Piotr Hogendorf, Adam Durczyński, Beata Smolarz
    Cancers.2025; 17(13): 2135.     CrossRef
  • Blood miRNAs miR-549a, miR-552, and miR-592 serve as potential disease-specific panels to diagnose colorectal cancer
    Soroush Akbar, Samaneh Mashreghi, Mohammad Reza Kalani, Akram Valanik, Farzaneh Ahmadi, Mahdi Aalikhani, Zahra Bazi
    Heliyon.2024; 10(7): e28492.     CrossRef
  • Integration of TE Induces Cancer Specific Alternative Splicing Events
    Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Woo Hyeon Bae, Du Hyeong Lee, Heui-Soo Kim
    International Journal of Molecular Sciences.2022; 23(18): 10918.     CrossRef
Article image
A comparative prognostic performance of definitions of Crohn-like lymphoid reaction in colorectal carcinoma
Younghoon Kim, Jeong Mo Bae, Jung Ho Kim, Nam-Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2021;55(1):53-59.   Published online November 27, 2020
DOI: https://doi.org/10.4132/jptm.2020.10.06
  • 6,334 View
  • 148 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary Material
Background
The prognostic potential of Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) has been investigated through the assessment of different criteria.
Methods
The prognostic impact of CLR was investigated in 636 CRC patients to compare methods from previously published articles. These methods included CLR measured by number of lymphoid aggregates (LAs) (CLR count), LA size greater than or equal to 1 mm (CLR size), CLR density with a cutoff value of 0.38, and subjective criteria as defined by intense CLR.
Results
In univariate survival analysis, CLR-positive CRC as defined by the four aforementioned methods was associated with better overall survival (OS) (hazard ratio [HR], 0.463; 95% confidence interval [CI], 0.305 to 0.702; p <.001; HR, 0.656; 95% CI, 0.411 to 1.046; p=.077; HR, 0.363; 95% CI, 0.197 to 0.669; p=.001; and HR, 0.433; 95% CI, 0.271 to 0.690; p<.001, respectively) and disease-free survival (DFS) (HR, 0.411; 95% CI, 0.304 to 0.639; p<.001; HR, 0.528; 95% CI, 0.340 to 0.821; p=.004; HR, 0.382; 95% CI, 0.226 to 0.645, p=.004; and HR, 0.501; 95% CI, 0.339 to 0.741; p<.001, respectively) than CLR-negative CRC, regardless of criteria with the exception of OS for CLR density. In multivariate analysis, two objective criteria (CLR count and CLR density) and one subjective criterion (intense CLR) for defining CLR were considered independent prognostic factors of OS and DFS in CRC patients.
Conclusions
CLR has similar traits regardless of criteria, but CLR-positivity should be defined by objective criteria for better reproducibility and prognostic value.

Citations

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  • Prognostic Significance of Immune and Stromal Components in Colorectal Cancer
    Mi Jang, Yongki Hong, Soojung Hong, Eun Kyung Kim
    Archives of Pathology & Laboratory Medicine.2025; 149(11): 982.     CrossRef
Reviews
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Immune landscape and biomarkers for immuno-oncology in colorectal cancers
Jeong Mo Bae, Seung-Yeon Yoo, Jung Ho Kim, Gyeong Hoon Kang
J Pathol Transl Med. 2020;54(5):351-360.   Published online June 26, 2020
DOI: https://doi.org/10.4132/jptm.2020.05.15
  • 10,263 View
  • 330 Download
  • 13 Web of Science
  • 14 Crossref
AbstractAbstract PDF
Recent advances in immuno-oncology have increased understanding of the tumor immune microenvironment (TIME), and clinical trials for immune checkpoint inhibitor treatment have shown remission and/or durable response in certain proportions of patients stratified by predictive biomarkers. The TIME in colorectal cancer (CRC) was initially evaluated several decades ago. The prognostic value of the immune response to tumors, including tumor-infiltrating lymphocytes, peritumoral lymphoid reaction, and Crohn’s-like lymphoid reaction, has been well demonstrated. In this review, we describe the chronology of TIME research and review the up-to-date high-dimensional TIME landscape of CRC. We also summarize the clinical relevance of several biomarkers associated with immunotherapy in CRC, such as microsatellite instability, tumor mutational burden, POLE/POLD mutation, consensus molecular subtype, and programmed death-ligand 1 expression.

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    Maode Lai
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    Moonsik Kim, Ji Yun Jeong, An Na Seo
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    Binshuang Zheng, Xiaoming Huang, Junyao Tang, Jiaying Chen, Runmin Zhao, Zhengqiang Hong, Tao Tang, Meiling Han, Yang Yang
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  • Intratumoral spatial heterogeneity of tumor-infiltrating lymphocytes is a significant factor for precisely stratifying prognostic immune subgroups of microsatellite instability-high colorectal carcinomas
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Article image
Evolving pathologic concepts of serrated lesions of the colorectum
Jung Ho Kim, Gyeong Hoon Kang
J Pathol Transl Med. 2020;54(4):276-289.   Published online June 26, 2020
DOI: https://doi.org/10.4132/jptm.2020.04.15
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AbstractAbstract PDFSupplementary Material
Here, we provide an up-to-date review of the histopathology and molecular pathology of serrated colorectal lesions. First, we introduce the updated contents of the 2019 World Health Organization classification for serrated lesions. The sessile serrated lesion (SSL) is a new diagnostic terminology that replaces sessile serrated adenoma and sessile serrated polyp. The diagnostic criteria for SSL were revised to require only one unequivocal distorted serrated crypt, which is sufficient for diagnosis. Unclassified serrated adenomas have been included as a new category of serrated lesions. Second, we review ongoing issues concerning the morphology of serrated lesions. Minor morphologic variants with distinct molecular features were recently defined, including serrated tubulovillous adenoma, mucin-rich variant of traditional serrated adenoma (TSA), and superficially serrated adenoma. In addition to intestinal dysplasia and serrated dysplasia, minimal deviation dysplasia and not otherwise specified dysplasia were newly suggested as dysplasia subtypes of SSLs. Third, we summarize the molecular features of serrated lesions. The critical determinant of CpG island methylation development in SSLs is patient age. Interestingly, there may be ethnic differences in BRAF/KRAS mutation frequencies in SSLs. The molecular pathogenesis of TSAs is divided into KRAS and BRAF mutation pathways. SSLs with MLH1 methylation can progress into favorable prognostic microsatellite instability-positive (MSI+)/CpG island methylator phenotype-positive (CIMP+) carcinomas, whereas MLH1-unmethylated SSLs and BRAF-mutated TSAs can be precursors of poor-prognostic MSI−/CIMP+ carcinomas. Finally, based on our recent data, we propose an algorithm for stratifying risk subgroups of non-dysplastic SSLs.

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Original Article
Article image
Colorectal epithelial neoplasm associated with gut-associated lymphoid tissue
Yo Han Jeon, Ji Hyun Ahn, Hee Kyung Chang
J Pathol Transl Med. 2020;54(2):135-145.   Published online January 29, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.06
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AbstractAbstract PDF
Background
Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term “GALT carcinoma” while other studies have mentioned the term “GALT-associated pseudoinvasion/epithelial misplacement (PEM)”.
Methods
The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.
Results
Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.
Conclusions
Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.

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Review
Article image
Standardized Pathology Report for Colorectal Cancer, 2nd Edition
Baek-hui Kim, Joon Mee Kim, Gyeong Hoon Kang, Hee Jin Chang, Dong Wook Kang, Jung Ho Kim, Jeong Mo Bae, An Na Seo, Ho Sung Park, Yun Kyung Kang, Kyung-Hwa Lee, Mee Yon Cho, In-Gu Do, Hye Seung Lee, Hee Kyung Chang, Do Youn Park, Hyo Jeong Kang, Jin Hee Sohn, Mee Soo Chang, Eun Sun Jung, So-Young Jin, Eunsil Yu, Hye Seung Han, Youn Wha Kim
J Pathol Transl Med. 2020;54(1):1-19.   Published online November 13, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.28
  • 28,857 View
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AbstractAbstract PDFSupplementary Material
The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

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Original Articles
Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma
Seung-Yeon Yoo, Ji-Ae Lee, Yunjoo Shin, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang
J Pathol Transl Med. 2019;53(5):289-297.   Published online June 24, 2019
DOI: https://doi.org/10.4132/jptm.2019.06.07
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AbstractAbstract PDFSupplementary Material
Background
SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC.
Methods
We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs.
Results
A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancerspecific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022).
Conclusions
We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.

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CpG Island Methylation in Sessile Serrated Adenoma/Polyp of the Colorectum: Implications for Differential Diagnosis of Molecularly High-Risk Lesions among Non-dysplastic Sessile Serrated Adenomas/Polyps
Ji Ae Lee, Hye Eun Park, Seung-Yeon Yoo, Seorin Jeong, Nam-Yun Cho, Gyeong Hoon Kang, Jung Ho Kim
J Pathol Transl Med. 2019;53(4):225-235.   Published online March 19, 2019
DOI: https://doi.org/10.4132/jptm.2019.03.12
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AbstractAbstract PDFSupplementary Material
Background
Although colorectal sessile serrated adenomas/polyps (SSA/Ps) with morphologic dysplasia are regarded as definite high-risk premalignant lesions, no reliable grading or risk-stratifying system exists for non-dysplastic SSA/Ps. The accumulation of CpG island methylation is a molecular hallmark of progression of SSA/Ps. Thus, we decided to classify non-dysplastic SSA/Ps into risk subgroups based on the extent of CpG island methylation.
Methods
The CpG island methylator phenotype (CIMP) status of 132 non-dysplastic SSA/Ps was determined using eight CIMP-specific promoter markers. SSA/Ps with CIMP-high and/or MLH1 promoter methylation were regarded as a high-risk subgroup.
Results
Based on the CIMP analysis results, methylation frequency of each CIMP marker suggested a sequential pattern of CpG island methylation during progression of SSA/P, indicating MLH1 as a late-methylated marker. Among the 132 non-dysplastic SSA/Ps, 34 (26%) were determined to be high-risk lesions (33 CIMP-high and 8 MLH1-methylated cases; seven cases overlapped). All 34 high-risk SSA/Ps were located exclusively in the proximal colon (100%, p = .001) and were significantly associated with older age (≥ 50 years, 100%; p = .003) and a larger histologically measured lesion size (> 5 mm, 100%; p = .004). In addition, the high-risk SSA/Ps were characterized by a relatively higher number of typical base-dilated serrated crypts.
Conclusions
Both CIMP-high and MLH1 methylation are late-step molecular events during progression of SSA/Ps and rarely occur in SSA/Ps of young patients. Comprehensive consideration of age (≥ 50), location (proximal colon), and histologic size (> 5 mm) may be important for the prediction of high-risk lesions among non-dysplastic SSA/Ps.

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Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy
Hyeon Jeong Oh, Jung Ho Kim, Jeong Mo Bae, Hyun Jung Kim, Nam-Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2019;53(1):40-49.   Published online December 26, 2018
DOI: https://doi.org/10.4132/jptm.2018.11.29
  • 19,598 View
  • 252 Download
  • 50 Web of Science
  • 53 Crossref
AbstractAbstract PDFSupplementary Material
Background
This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.
Methods
F. nucleatumDNA was quantitatively measured in a total of 593 CRC tissues retrospectively collectedfrom surgically resected specimens of stage III or high-risk stage II CRC patients who had receivedcurative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative.
Results
No significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses accordingto tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal,ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariateanalysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoidcolon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore,the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not ina MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor locationand MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treatedwith adjuvant chemotherapy.
Conclusions
Intratumoral F. nucleatum load is a potential prognosticfactor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treatedwith oxaliplatin-based adjuvant chemotherapy.

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Prognostic Significance of EPHB2 Expression in Colorectal Cancer Progression
Bo Gun Jang, Hye Sung Kim, Weon Young Chang, Jeong Mo Bae, Gyeong Hoon Kang
J Pathol Transl Med. 2018;52(5):298-306.   Published online July 18, 2018
DOI: https://doi.org/10.4132/jptm.2018.06.29
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AbstractAbstract PDF
Background
A receptor tyrosine kinase for ephrin ligands, EPHB2, is expressed in normal colorectal tissues and colorectal cancers (CRCs). The aim of this study was to investigate EPHB2 expression over CRC progression and determine its prognostic significance in CRC.
Methods
To measure EPHB2 mRNA and protein expression, real-time polymerase chain reaction and immunohistochemistry were performed in 32 fresh-frozen and 567 formalin-fixed paraffin-embedded CRC samples, respectively. We further investigated clinicopathological features and overall and recurrence-free survival according to EPHB2 protein expression.
Results
The EPHB2 level was upregulated in CRC samples compared to non-cancerous tissue in most samples and showed a strong positive correlation with AXIN2. Notably, CD44 had a positive association with both mRNA and protein levels of EPHB2. Immunohistochemical analysis revealed no difference in EPHB2 expression between adenoma and carcinoma areas. Although EPHB2 expression was slightly lower in invasive fronts compared to surface area (p < .05), there was no difference between superficial and metastatic areas. EPHB2 positivity was associated with lymphatic (p < .001) and venous (p = .001) invasion, TNM stage (p < .001), and microsatellite instability (p = .036). Kaplan–Meier analysis demonstrated that CRC patients with EPHB2 positivity showed better clinical outcomes in both overall (p = .049) and recurrence-free survival (p = .015). However, multivariate analysis failed to show that EPHB2 is an independent prognostic marker in CRCs (hazard ratio, 0.692; p = .692).
Conclusions
Our results suggest that EPHB2 is overexpressed in a subset of CRCs and is a significant prognostic marker.

Citations

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  • High levels of EPHB2 expression predict a poor prognosis and promote tumor progression in endometrial cancer
    Yanlai Xiao, Jian Wang, Xiangzhai Zhao, Jie Xu, Huan Zhao, Zhaojun Guo, Jun Zhao, Yajing Zhang, Ruoxi Wang, Yiwei Zhang
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  • Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets
    João Figueira Scarini, Moisés Willian Aparecido Gonçalves, Reydson Alcides de Lima-Souza, Luccas Lavareze, Talita de Carvalho Kimura, Ching-Chu Yang, Albina Altemani, Fernanda Viviane Mariano, Heloisa Prado Soares, Gary Chris Fillmore, Erika Said Abu Egal
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    Shengshan Xu, Youbin Zheng, Min Ye, Tao Shen, Dongxi Zhang, Zumei Li, Zhuming Lu
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  • Therapeutic effects of ephrin B receptor 2 inhibitors screened by molecular docking on cutaneous squamous cell carcinoma
    Yan Li, Xuanfen Zhang
    Journal of Dermatological Treatment.2022; 33(1): 373.     CrossRef
  • The EPH/Ephrin System in Colorectal Cancer
    Stavros P. Papadakos, Leonidas Petrogiannopoulos, Alexandros Pergaris, Stamatios Theocharis
    International Journal of Molecular Sciences.2022; 23(5): 2761.     CrossRef
  • Prognostic Significance of Autophagy-Relevant Gene Markers in Colorectal Cancer
    Qinglian He, Ziqi Li, Jinbao Yin, Yuling Li, Yuting Yin, Xue Lei, Wei Zhu
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    Bahar Dasgeb, Leila Youssefian, Amir Hossein Saeidian, Jun Kang, Wenyin Shi, Elizabeth Shoenberg, Adam Ertel, Paolo Fortina, Hassan Vahidnezhad, Jouni Uitto
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Utility of BRAF VE1 Immunohistochemistry as a Screening Tool for Colorectal Cancer Harboring BRAF V600E Mutation
Jeong-Hwa Kwon, Byung-Kwan Jeong, Yong Sik Yoon, Chang Sik Yu, Jihun Kim
J Pathol Transl Med. 2018;52(3):157-163.   Published online March 29, 2018
DOI: https://doi.org/10.4132/jptm.2018.03.28
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AbstractAbstract PDFSupplementary Material
Background
BRAF mutation has been recognized as an important biomarker of colorectal cancer (CRC) for targeted therapy and prognosis prediction. However, sequencing for every CRC case is not cost-effective. An antibody specific for BRAF V600E mutant protein has been introduced, and we thus examined the utility of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC.
Methods
Fifty-one BRAF-mutated CRCs and 100 age and sexmatched BRAF wild-type CRCs between 2005 and 2015 were selected from the archives of Asan Medical Center. Tissue microarrays were constructed and stained with BRAF VE1 antibody.
Results
Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate cytoplasmic staining, except for two weakly stained cases. Six of 100 BRAF wild-type cases also stained positive with BRAF VE1 antibody; four stained weakly and two stained moderately. Normal colonic crypts showed nonspecific weak staining, and a few CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10 BRAF wild-type cases). BRAF-mutated CRC patients had higher pathologic stages and worse survival than BRAF wild-type patients.
Conclusions
BRAF VE1 immunohistochemistry showed high sensitivity and specificity, but occasional nonspecific staining in tumor cell nuclei and normal colonic crypts may limit their routine clinical use. Thus, BRAF VE1 immunohistochemistry may be a useful screening tool for BRAF V600E mutation in CRCs, provided that additional sequencing studies can be done to confirm the mutation in BRAF VE1 antibody-positive cases.

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  • Next-Generation Sequencing in Oncology—A Guiding Compass for Targeted Therapy and Emerging Applications
    Laurenția Nicoleta Galeș, Mihai-Andrei Păun, Ioana Butnariu, Laurentiu Simion, Loredana Sabina Cornelia Manolescu, Oana Gabriela Trifănescu, Rodica Maricela Anghel
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Prognostic Utility of Histological Growth Patterns of Colorectal Lung Oligometastasis
Son Jae Yeong, Min Gyoung Pak, Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh
J Pathol Transl Med. 2018;52(2):98-104.   Published online February 12, 2018
DOI: https://doi.org/10.4132/jptm.2017.12.27
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  • 3 Web of Science
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AbstractAbstract PDF
Background
Patients with resectable colorectal lung oligometastasis (CLOM) demonstrate a heterogeneous oncological outcome. However, the parameters for predicting tumor aggressiveness have not yet been fully investigated in CLOM. This study was performed to determine the prognostic value of histological growth patterns in patients who underwent surgery for CLOM.
Methods
The study included 92 patients who were diagnosed with CLOM among the first resection cases. CLOMs grow according to three histological patterns: aerogenous, pushing, and desmoplastic patterns. The growth patterns were evaluated on archival hematoxylin and eosin–stained tissue sections.
Results
The aerogenous pattern was found in 29.4% (n=27) of patients, the pushing pattern in 34.7% (n=32), the desmoplastic pattern in 6.5% (n=6), and a mix of two growth patterns in 29.4% (n=27). The size of the aerogenous pattern was significantly smaller than that of metastases with other patterns (p=.033). Kaplan-Meier analysis demonstrated that patients showing an aerogenous pattern appeared to have a poorer prognosis, which was calculated from the time of diagnosis of the CLOM (p=.044). The 5-year survival rate from the diagnosis of colorectal cancer tended to be lower in patients with an aerogenous pattern than in those who had a non-aerogenous pattern; however, the difference was marginally significant (p=.051). In the multivariate Cox analysis, the aerogenous pattern appeared as an independent predictor of poor overall survival (hazard ratio, 3.122; 95% confidence interval, 1.196 to 8.145; p=.020).
Conclusions
These results suggest that the growth patterns may play a part as a histology-based prognostic parameter for patients with CLOM.

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  • Predicting liver metastases growth patterns: Current status and future possibilities
    Rui Caetano Oliveira, Henrique Alexandrino, Maria Augusta Cipriano, Filipe Caseiro Alves, José Guilherme Tralhão
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Overexpression of POSTN in Tumor Stroma Is a Poor Prognostic Indicator of Colorectal Cancer
Hyeon Jeong Oh, Jeong Mo Bae, Xian-Yu Wen, Nam-Yun Cho, Jung Ho Kim, Gyeong Hoon Kang
J Pathol Transl Med. 2017;51(3):306-313.   Published online April 12, 2017
DOI: https://doi.org/10.4132/jptm.2017.01.19
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  • 48 Web of Science
  • 45 Crossref
AbstractAbstract PDF
Background
Tumor microenvironment has recently drawn attention in that it is related with tumor prognosis. Cancer-associated fibroblast also plays a critical role in cancer invasiveness and progression in colorectal cancers. Periostin (POSTN), originally identified to be expressed in osteoblasts and osteoblast-derived cells, is expressed in cancer-associated fibroblasts in several tissue types of cancer. Recent studies suggest an association between stromal overexpression of POSTN and poor prognosis of cancer patients.
Methods
We analyzed colorectal cancer cases for their expression status of POSTN in tumor stroma using immunohistochemistry and correlated the expression status with clinicopathological and molecular features.
Results
High level of POSTN expression in tumor stroma was closely associated with tumor location in proximal colon, infiltrative growth pattern, undifferentiated histology, tumor budding, luminal necrosis, and higher TNM stage. High expression status of POSTN in tumor stroma was found to be an independent prognostic parameter implicating poor 5-year cancer-specific survival and 5-year progression-free survival.
Conclusions
Our findings suggest that POSTN overexpression in tumor stroma of colorectal cancers could be a possible candidate marker for predicting poor prognosis in patients with colorectal cancers.

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Review
Article image
Molecular Testing for Gastrointestinal Cancer
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y. Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
J Pathol Transl Med. 2017;51(2):103-121.   Published online February 19, 2017
DOI: https://doi.org/10.4132/jptm.2017.01.24
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AbstractAbstract PDF
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

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Original Articles
Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry
Jiyoon Jung, Youngjin Kang, Yoo Jin Lee, Eojin Kim, Bokyung Ahn, Eunjung Lee, Joo Young Kim, Jeong Hyeon Lee, Youngseok Lee, Chul Hwan Kim, Yang-Seok Chae
J Pathol Transl Med. 2017;51(2):129-136.   Published online February 14, 2017
DOI: https://doi.org/10.4132/jptm.2016.12.09
  • 12,442 View
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AbstractAbstract PDF
Background
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%–15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses. Methods: In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined. Results: Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor. Conclusions: Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

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Article image
Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer
Wanlu Li, Mi-Ra Lee, EunHee Choi, Mee-Yon Cho
J Pathol Transl Med. 2017;51(1):17-23.   Published online December 15, 2016
DOI: https://doi.org/10.4132/jptm.2016.09.23
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AbstractAbstract PDF
Background
Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples.
Methods
We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling.
Results
The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133+ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133+ versus 4.231 ± 3.812 in CD133– (p = .034).
Conclusions
As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC.

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CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance
Kyung-Ju Kim, Hee Jung Kwon, Min Chong Kim, Young Kyung Bae
J Pathol Transl Med. 2016;50(6):459-468.   Published online October 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.10.02
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AbstractAbstract PDF
Background
CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression.
Methods
The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression.
Results
High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan- Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054).
Conclusions
High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs.

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Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases
Kyu Sang Lee, Soo Kyung Nam, Jiwon Koh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
J Pathol Transl Med. 2016;50(4):270-277.   Published online May 31, 2016
DOI: https://doi.org/10.4132/jptm.2016.03.19
  • 10,624 View
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  • 21 Web of Science
  • 17 Crossref
AbstractAbstract PDF
Background
The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
Methods
miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
Results
The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
Conclusions
miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.

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Eosinophils in Colorectal Neoplasms Associated with Expression of CCL11 and CCL24
Hyuck Cho, Sung-Jig Lim, Kyu Yeoun Won, Go Eun Bae, Gou Young Kim, Ji Won Min, Byeong-joo Noh
J Pathol Transl Med. 2016;50(1):45-51.   Published online December 14, 2015
DOI: https://doi.org/10.4132/jptm.2015.10.16
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AbstractAbstract PDF
Background
A decrease in the number of tissue eosinophils is known to reflect the malignancy potential of neoplastic lesions and even prognosis. Increased levels of the chemokines CCL11 and CCL24 in serum and tissue are also known to have diagnostic value as serum tumor markers or prognostic factors. The aim of this study was to evaluate the correlation between the degree of tissue eosinophilia and the expression of these chemokines in the glandular and stromal cells of colorectal neoplastic lesions ranging from benign to malignant tumors. Methods: We counted the number of infiltrating eosinophils in neoplastic lesion tissue and we evaluated the expression of CCL11 and CCL24 in glandular cells and stromal cells by immunohistochemical staining. Results: The results showed that the number of eosinophils decreased significantly and the expression of CCL11 and CCL24 in glandular cells decreased with tumor progression, whereas the stromal expression of CCL11 and CCL24 appeared to increase. Conclusions: The discrepancy in CCL11 and CCL24 expression between glandular cells and stromal cells might shed light on how colorectal cancer evades the immune system, which would enable further development of immunotherapies that target these chemokines. Further research on eosinophil biology and the expression pattern of chemokines in tumor cells is needed.

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Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers
Jung Ho Kim, Jeong Mo Bae, Hyeon Jeong Oh, Hye Seung Lee, Gyeong Hoon Kang
J Pathol Transl Med. 2015;49(2):118-128.   Published online March 12, 2015
DOI: https://doi.org/10.4132/jptm.2015.02.05
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AbstractAbstract PDF
Background
Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability–high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet. Methods: A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS). Results: Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin–based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin–based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy. Conclusions: pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC.

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Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status
Jung Ho Kim, Jeong Mo Bae, Kyung-Ju Kim, Ye-Young Rhee, Younghoon Kim, Nam-Yun Cho, Hye Seung Lee, Mee Soo Chang, Gyeong Hoon Kang
Korean J Pathol. 2014;48(4):276-282.   Published online August 26, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.276
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AbstractAbstract PDF
Background

Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs.

Methods

Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight).

Results

Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004).

Conclusions

Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.

Citations

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Progressive Increase of Regulatory T Cells and Decrease of CD8+ T Cells and CD8+ T Cells/Regulatory T Cells Ratio during Colorectal Cancer Development
Tae Jung Jang
Korean J Pathol. 2013;47(5):443-451.   Published online October 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.443
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AbstractAbstract PDF
Background

We examined the distribution of CD8+ T cells and regulatory T cells (Tregs), measured the CD8+ T cell/Tregs ratio, investigated the relationship between Tregs and cyclooxygenase-2 (COX-2) expression during colorectal cancer (CRC) development.

Methods

We performed immunohistochemical staining for CD8, forkhead box P3, E-cadherin, and COX-2 in 32 cases of invasive CRC, 10 cases of intramucosal CRC, 27 cases of high-grade tubular adenoma, 22 cases of low-grade tubular adenoma, and 32 cases of non-neoplastic conditions.

Results

We observed a progressive increase in Tregs, and a decrease in CD8+ T cells and the CD8+ T cells/Tregs ratio during CRC development. The alterations were most severe in high-grade tubular adenoma and CRC. COX-2 expression was positively associated with Tregs infiltration. The degree of T cell infiltration differed among tumor compartment and the ratio in the tumor center was the lowest of all areas. The ratio and number of CD8+ T cells in the tumor center and the invasive front of invasive CRC were associated with gender, differentiation, node metastasis and tumor budding.

Conclusions

Alteration in the distribution of both CD8+T cells and Tregs may contribute to the generation of an immune environment suitable for the development and progression of CRC.

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The Expression of CD10 and CD15 Is Progressively Increased during Colorectal Cancer Development
Tae Jung Jang, Jeong Bae Park, Jong Im Lee
Korean J Pathol. 2013;47(4):340-347.   Published online August 26, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.340
  • 12,399 View
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AbstractAbstract PDF
Background

The aim of this study was to examine the expression of CD10 and CD15 in tumor cells, stromal cells and infiltrating inflammatory cells during colorectal carcinoma (CRC) development and to investigate their expression levels between the tumor center and invasive front and compare them to clinicopathological parameters in invasive CRC.

Methods

We performed immunohistochemical staining for CD10, CD15, and E-cadherin in 42 cases of CRC, 49 of tubular adenoma, 15 of hyperplastic polyp, and 17 of non-neoplastic colon.

Results

CD10 was expressed in tumor cells (tCD10), stromal cells (sCD10) and infiltrating inflammatory cells (iCD10), and CD15 was expressed in tumor cells (tCD15) and infiltrating inflammatory cells (iCD15). Their expressions were progressively increased during CRC development and the iCD10 expression level was significantly correlated with the iCD15 expression level in invasive CRC. Invasive front revealed a higher expression level of iCD10 and iCD15 than the tumor center. Moreover, the iCD15 expression level of invasive front was significantly correlated with the degree of tumor budding and tCD15 in whole tissue sections was closely associated with tumor depth.

Conclusions

The present study suggests that the expression of CD10 and CD15 is associated with the development and progression of CRC.

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Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis
Yun Kyung Kang, So-Young Jin, Mee Soo Chang, Jung Yeon Kim, Gyeong Hoon Kang, Hye Seung Lee, Jin Hee Sohn, Ho Sung Park, Kye Won Kwon, Mi Jin Gu, Young Hee Maeng, Jong Eun Joo, Haeng Ji Kang, Hee Kyung Kim, Kee-Taek Jang, Mi Ja Lee, Hee Kyung Chang, Joon Mee Kim, Hye Seung Han, Won Ae Lee, Yoon Jung Choi, Dong Wook Kang, Sunhoo Park, Jae Hyuk Lee, Mee-Yon Cho
Korean J Pathol. 2013;47(3):245-251.   Published online June 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.245
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AbstractAbstract PDF
Background

The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.

Methods

We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.

Results

The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.

Conclusions

Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.

Citations

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Review
Radiotherapy Response in Microsatellite Instability Related Rectal Cancer
Joo-Shik Shin, Thein Ga Tut, Tao Yang, C. Soon Lee
Korean J Pathol. 2013;47(1):1-8.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.1
  • 12,102 View
  • 99 Download
  • 31 Crossref
AbstractAbstract PDF

Preoperative radiotherapy may improve the resectability and subsequent local control of rectal cancers. However, the extent of radiation induced regression in these tumours varies widely between individuals. To date no reliable predictive marker of radiation sensitivity in rectal cancer has been identified. At the cellular level, radiation injury initiates a complex molecular network of DNA damage response (DDR) pathways that leads to cell cycle arrest, attempts at re-constituting the damaged DNA and should this fail, then apoptosis. This review presents the details which suggest the roles of DNA mismatch repair proteins, the lack of which define a distinct subset of colorectal cancers with microsatellite instability (MSI), in the DDR pathways. Hence routine assessment of the MSI status in rectal cancers may potentially serve as a predictor of radiotherapy response, thereby improving patient stratification in the administration of this otherwise toxic treatment.

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Original Article
Expression of Cortactin and Focal Adhesion Kinase in Colorectal Adenocarcinoma: Correlation with Clinicopathologic Parameters and Their Prognostic Implication
Yo Na Kim, Ji Eun Choi, Jun Sang Bae, Kyu Yun Jang, Myoung Ja Chung, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Ho Sung Park
Korean J Pathol. 2012;46(5):454-462.   Published online October 25, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.454
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AbstractAbstract PDF
Background

Cortactin and focal adhesion kinase (FAK) are two important components among actin cross-linking proteins that play a central role in cell migration.

Methods

The aims of this study were to evaluate the expression of cortactin and FAK in normal colorectal mucosa and colorectal adenocarcinoma (CRC) using tissue microarray of 2 mm cores to correlate their expression with other clinicopathological factors and, investigate their prognostic significance.

Results

Twenty (9%) and 24 cases (11%) of normal colorectal mucosa were immunoreactive for cortactin and FAK. In addition, 184 (84%) and 133 cases (61%) of CRCs were immunoreactive for cortactin and FAK, respectively. Cortactin expression was associated with histologic differentiation and FAK expression. Cortactin, but not FAK expression was also correlated with poor overall and relapse-free survival and served well as an independent prognostic factor for poor survival.

Conclusions

Cortactin expression, in association with FAK expression, may plays an important role in tumor progression. Furthermore, it may also be a satisfactory biomarker to predict tumor progression and survival in CRC patients.

Citations

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Case Report
Tumor Budding and Recurrence in Submucosal Invasive Colorectal Cancers of Favorable Histology: Case Reports of Two Early Colorectal Cancers with Advanced Recurrences
Heae Surng Park, Hee Jin Chang, Ji Won Park, Byung Chang Kim, Dae Kyung Sohn, Chang Won Hong, Ji-Yeon Baek, Sun Young Kim, Hyo Seong Choi, Jae Hwan Oh
Korean J Pathol. 2012;46(3):272-277.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.272
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AbstractAbstract PDF

Complete resection of submucosal invasive colorectal cancer (SICC) showing favorable histology is regarded as curative. We report on two cases of SICC showing recurrence within 5 years despite complete resection. The first patient was a 68-year-old woman with well differentiated rectal adenocarcinoma invading the superficial submucosa, which recurred after 4.7 years. The second patient was a 53-year-old man with pT1N0 moderately differentiated colonic adenocarcinoma. He developed widespread tumor recurrence after 3.9 years. Retrospective pathologic review of the original tumors showed multiple foci of tumor budding at the invasive front. Immunohistochemical staining for D2-40 of deeper levels of the paraffin blocks showed rare foci of small lymphatic invasion. Tumor budding at the invasive front may be an important indicator for SICC aggressiveness or may reflect early lymphatic invasion. More aggressive pathologic examination and follow-up is required for patients with SICC showing tumor budding, even in the absence of unfavorable histologic findings.

Citations

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Original Articles
Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma.
Kyung Hwa Lee, Soong Lee, Hyeon Min Lee, Seung Chul Back, Sung Bum Cho, Jae Hyuk Lee
Korean J Pathol. 2011;45(4):397-405.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.397
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AbstractAbstract PDF
BACKGROUND
The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance.
METHODS
Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method.
RESULTS
Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041).
CONCLUSIONS
Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

Citations

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  • A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer
    Pierina Cetraro, Julio Plaza-Diaz, Alex MacKenzie, Francisco Abadía-Molina
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Rapid and Sensitive Detection of KRAS Mutation by Peptide Nucleic Acid-based Real-time PCR Clamping: A Comparison with Direct Sequencing between Fresh Tissue and Formalin-fixed and Paraffin Embedded Tissue of Colorectal Cancer.
Dongjun Jeong, Yujun Jeong, Jonghyun Lee, Moo Jun Baek, Yongbae Kim, Ji Hye Lee, Hyun Deuk Cho, Mee Hye Oh, Chang Jin Kim
Korean J Pathol. 2011;45(2):151-159.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.151
  • 6,027 View
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  • 8 Crossref
AbstractAbstract PDF
BACKGROUND
Rapid and sensitive detection of KRAS mutation is needed to maximize the benefits for patients who are being treated with monoclonal antibodies to target the epidermal growth factor receptor in colorectal cancer. The aim of this study is to evaluate the efficacy of the peptide nucleic acid clamp real-time PCR (PCqPCR) as compared to that of direct sequencing (DS) between using fresh colorectal cancer tissue and the matched formalin-fixed and paraffin-embedded (FFPE) colorectal cancer tissue.
METHODS
The efficacy of PCqPCR was evaluated and compared with that of DS using fresh tissue and matched FFPE tissue from 30 cases of colorectal cancer.
RESULTS
PCqPCR is more sensitive than DS for detecting KRAS mutation. PCqPCR detected 1% of mutants in 1 ng DNA. PCqPCR detected mutation in 1% of mutant cells, while DS barely detected, by manual reading, that in 20-50% of mutant cells. In the clinical samples, PCqPCR detected KRAS mutation in 60.0% while DS detected KRAS mutation in 53.3% of the colorectal cancers. The two methods showed a 100% concordance rate for detecting KRAS mutation between the fresh tissue and FFPE tissue.
CONCLUSIONS
The PCqPCR method is efficiently applicable for the detection of KRAS mutation in a clinical setting.

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  • NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions
    Jung Ho Kim, Jeong Hoon Hong, Yoon‐La Choi, Ji Ae Lee, Mi‐kyoung Seo, Mi‐Sook Lee, Sung Bin An, Min Jung Sung, Nam‐Yun Cho, Sung‐Su Kim, Young Kee Shin, Sangwoo Kim, Gyeong Hoon Kang
    The Journal of Pathology.2021; 255(4): 399.     CrossRef
  • Discrimination of the V600E Mutation in BRAF by Rolling Circle Amplification and Förster Resonance Energy Transfer
    Mariia Dekaliuk, Xue Qiu, Frédéric Troalen, Pierre Busson, Niko Hildebrandt
    ACS Sensors.2019; 4(10): 2786.     CrossRef
  • Sensitive Genotyping of Somatic Mutations in the EGFR, KRAS, PIK3CA, BRAF Genes from NSCLC Patients Using Hydrogel Biochips
    Marina Emelyanova, Ksenia Arkhipova, Natalia Mazurenko, Alexander Chudinov, Irina Demidova, Irina Zborovskaya, Lyudmila Lyubchenko, Alexander Zasedatelev, Tatiana Nasedkina
    Applied Immunohistochemistry & Molecular Morphology.2015; 23(4): 255.     CrossRef
  • Low Frequency of KRAS Mutation in Pancreatic Ductal Adenocarcinomas in Korean Patients and Its Prognostic Value
    Mi Jung Kwon, Jang Yong Jeon, Hye-Rim Park, Eun Sook Nam, Seong Jin Cho, Hyung Sik Shin, Ji Hyun Kwon, Joo Seop Kim, Boram Han, Dong Hoon Kim, Yoon-La Choi
    Pancreas.2015; 44(3): 484.     CrossRef
  • Comparison of PNA clamping and direct sequencing for detecting KRAS mutations in matched tumour tissue, cell block, pleural effusion and serum from patients with malignant pleural effusion
    Ji Young Kang, Chan Kwon Park, Chang Dong Yeo, Hea Yeon Lee, Chin Kook Rhee, Seung Joon Kim, Seok Chan Kim, Young Kyoon Kim, Mi Sun Park, Hyeon Woo Yim
    Respirology.2015; 20(1): 138.     CrossRef
  • BRAF V600E Mutation Analysis in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-time PCR
    Dongjun Jeong, Yujun Jeong, Ji Hye Park, Sun Wook Han, Sung Yong Kim, Yeo Joo Kim, Sang Jin Kim, Young Hwangbo, Soyoung Park, Hyun Deuk Cho, Mee Hye Oh, Seung Ha Yang, Chang Jin Kim
    Annals of Surgical Oncology.2013; 20(3): 759.     CrossRef
  • Detection and comparison of EGFR mutations in matched tumor tissues, cell blocks, pleural effusions, and sera from patients with NSCLC with malignant pleural effusion, by PNA clamping and direct sequencing
    Chang Dong Yeo, Jin Woo Kim, Kwan Hyoung Kim, Jick Hwan Ha, Chin Kook Rhee, Seung Joon Kim, Young Kyoon Kim, Chan Kwon Park, Sang Haak Lee, Mi Sun Park, Hyeon Woo Yim
    Lung Cancer.2013; 81(2): 207.     CrossRef
  • Detection ofBRAFV600EMutations in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-Time PCR: A Comparison with Direct Sequencing
    Dongjun Jeong, Yujun Jeong, Sungche Lee, Hyeran Lee, Wanju Lee, Hyungjoo Kim, Doosan Park, Soyoung Park, Wenxia Mu, Hyun-Deuk Cho, Mee-Hye Oh, Sung Soo Lee, Seung-Ha Yang, Chang-Jin Kim
    Korean Journal of Pathology.2012; 46(1): 61.     CrossRef
Validation of Gene Expression Changes of Osteopontin and MMP-1 in Primary and Metastatic Colorectal Carcinomas.
Junjeong Choi, Sangkyum Kim, Jeon Han Park, Nam Kyu Kim, Hoguen Kim
Korean J Pathol. 2010;44(3):225-233.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.225
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AbstractAbstract PDF
BACKGROUND
Metastasis is one of the most important characteristics of cancer in terms of its impact on patient survival. Unfortunately, identification of altered genes during tumor metastasis is limited.
METHODS
Using high-throughput microarrays containing 19K spotted human oligonucleotides, gene expression of primary and matched metastatic colon cancer were compared in previous study. Although DNA microarray analysis did not demonstrate complete classification of primary and metastatic carcinoma, 80 differentially expressed genes were identified. Among these, expression of osteopontin, matrix metalloproteinase-1 (MMP-1) and serpin A1 was assessed using immunohistochemistry in a validation set containing 43 pairs from tissue microarrays.
RESULTS
The expression of osteopontin was significantly higher in metastatic carcinoma than in primary carcinoma, as indicated by mRNA expression. The expression of MMP-1 was significantly lower in metastatic carcinoma. Expression of serpin A1 was not correlated with the microarray results.
CONCLUSIONS
Osteopontin and MMP-1 expression successfully classified primary and metastatic colorectal carcinomas and further studies on their clinical application is encouraged.
Aberrant Promoter Methylation of the Vimentin Gene in Colorectal Cancer Associated with the Adenoma-Carcinoma Sequence.
Mi Hee Cho, Yu Mi Lee, Jin Sook Kim, Hyun Soo Kim, Kyung Hwa Lee, Sang Woo Juhng, Jae Hyuk Lee
Korean J Pathol. 2010;44(2):179-186.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.179
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  • 2 Crossref
AbstractAbstract PDF
BACKGROUND
DNA hypermethylation is a common epigenetic finding in human cancers and is closely associated with transcriptional silencing. In the present study, we investigated the proportion of colorectal neoplasms that showed the adenoma-carcinoma progression and vimentin gene methylation.
METHODS
Methylation status of the vimentin gene was examined in nontumoral mucosa, adenomas, and adenocarcinomas from 45 colorectal cancer patients who had adenoma and adenocarcinoma together. Methylation status was determined by bisulfite modification and the methylation-specific polymerase chain reaction. The expression of the vimentin gene product was also examined by immunohistochemistry.
RESULTS
Promoter methylation of vimentin was detected in 80% (36 out of 45 cases) of adenocarcinomas, 82.2% (37 of 45) of adenomas, and 28.9% (13 of 45) of normal epithelia, and the difference between neoplastic and normal specimens was statistically significant (p < 0.001). However, no significant correlations were observed between methylation frequency and clinicopathologic variables. Immunohistochemically, vimentin expression was not observed in either normal epithelial cells or tumor cells. Protein expression and vimentin promoter methylation were not associated.
CONCLUSIONS
The frequency of aberrant methylation of the vimentin gene was high in colonic adenomas and adenocarcinomas. This result suggests that the methylation status of vimentin may be clinically beneficial in screening for colorectal cancer patients and may be helpful in clarifying colorectal cancer biology.

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  • Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum
    Margaret Thomas, Paola Marcato
    Cancers.2018; 10(4): 101.     CrossRef
  • Aberrant promoter methylation of beta‐1,4 galactosyltransferase 1 as potential cancer‐specific biomarker of colorectal tumors
    Maria Luana Poeta, Emanuela Massi, Paola Parrella, Pasquale Pellegrini, Mariangela De Robertis, Massimiliano Copetti, Carla Rabitti, Giuseppe Perrone, Andrea Onetti Muda, Francesca Molinari, Elena Zanellato, Stefano Crippa, Damiano Caputo, Marco Caricato,
    Genes, Chromosomes and Cancer.2012; 51(12): 1133.     CrossRef
Clinicopathologic Significances of EGFR Expression at Invasive Front of Colorectal Cancer.
Yeo Ju Kang, Chan Kwon Jung, Yeong Jin Choi, Kyo Young Lee, Hyung Jin Kim, Won Kyung Kang, Seong Taek Oh
Korean J Pathol. 2010;44(1):16-21.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.16
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AbstractAbstract PDF
BACKGROUND
Epidermal growth factor receptor (EGFR) is frequently expressed in the invasive front of colorectal cancer (CRC), but its clinicopathologic significance remains unclear. We investigated the clinical value of the EGFR expression at the invasive front of CRC.
METHODS
We performed an immunohistochemical analysis in order to examine the expression and distribution of EGFR in 214 cases of CRC. The EGFR status was considered positive when > or =1% of the tumor cells had membranous staining.
RESULTS
Overall, an EGFR expression was observed in 144 (67%) cases and it had no significant relationship with the clinicopathologic parameters. However, an EGFR expression at the invasive front was correlated with lymphatic invasion, lymph node metastasis and a high level of serum carcinoembryonic antigen (p = 0.028, p = 0.043, and p = 0.045, respectively). For the budding-positive CRCs liver metastases were found in the cases with an EGFR expression at the budding, but no liver metastasis occurred in the EGFR negative cases at the budding (p = 0.030).
CONCLUSIONS
An EGFR expression at the invasive front has clinicopathologic significances in patients with CRC. An EGFR expression at tumor cell budding is a pathologic marker that suggests the high potential for liver metastasis in CRC.
Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability.
Sang Kyum Kim, Junjeong Choi, Hyun Ki Kim, Young Nyun Park, Si Young Song, Hoguen Kim
Korean J Pathol. 2009;43(5):428-434.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.428
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes.
METHODS
We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes.
RESULTS
MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs.
CONCLUSIONS
These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.

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  • Fibroblast Growth Factor Receptor 1 Gene Copy Number and mRNA Expression in Primary Colorectal Cancer and Its Clinicopathologic Correlation
    Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Duck-Woo Kim, Sung-Bum Kang, Woo Ho Kim, Hye Seung Lee
    Pathobiology.2015; 82(2): 76.     CrossRef
Microsatellite Instability in Colorectal Carcinomas.
Hee Jeong Cha, Dong Kyun Woo, Sun Hee Kim, Yong ll Kim, Jae Gahb Park, Woo Ho Kim
Korean J Pathol. 2001;35(2):111-114.
  • 2,180 View
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AbstractAbstract PDF
BACKGROUND
Microsatellite instability (MSI), which is caused by a deficient mismatch repair system, is seen in most of the hereditary non-polyposis colon cancers and a portion of sporadic colorectal cancers.
METHODS
Two hundreds forty-six consecutive sporadic colorectal cancer patients were analyzed for MSI using an ABI 377 automatic sequencer and fluorescent dye-labelled primers (BAT-25 and BAT-26).
RESULTS
The overall incidence of MSI in studied cases was 9.8% (24/246). This incidence is lower than most of the reported incidences in western countries. The incidence of MSI tumors in the proximal colon was 29.6%, while that of the distal colon was only 4.2% (p<0.001). MSI in sporadic colorectal cancers was more prevalent in poorly differentiated adenocarcinoma. In contrast to western countries, mucinous carcinoma did not show higher incidence of MSI.
CONCLUSION
The results suggest that MSI frequently occurs in cancers of the proximal colon and in tumors with poorly differentiated histology.
The Expression of Transforming Growth Factor-1 and Its Signaling Receptors in Human Colorectal Carcinoma.
Gyeong Seon Kim, Joo Heon Kim, Woo Sung Moon, Myoung Ja Chung, Dong Geun Lee, Myoung Jae Kang
Korean J Pathol. 2001;35(2):115-122.
  • 2,061 View
  • 14 Download
AbstractAbstract PDF
BACKGROUND
Resistance to the potent growth inhibitory effects of TGF- (transforming growth factor-) is a characteristic of many malignancies. TGF- insensitivity has been attributed to alterations in the number and function of the TGF- receptors as well as disturbances of downstream signal transduction. The aim of this study was to examine the expression of TGF-1 and its receptors in human colorectal cancer tissue and determine its relationship with cancer growth and with prognostic factors.
METHODS
Immunohistochemical staining of TGF-1, TGF-RI, and TGF-RII was performed on 20 human colorectal adenomas, 30 carcinomas and 10 normal mucosas as a control.
RESULTS
The staining indices of TGF-1, TGF-RI, and TGF-RII increased in adenomas and carcinomas compared with normal mucosas and adenomas, respectively. In adenomas the staining index of TGF-1 significantly increased with the severity of atypism. The staining index of TGF-RII increased in the carcinomas in the right colon and rectum, compared with those in the left colon.
CONCLUSION
The enhanced expression of TGF-1, TGF-RI and II in the colorectal carcinoma suggests an important role of colorectal carcinogenesis and tumor progression.
Epidermal Growth Factor Receptor Overexpression and the Tumor Response to Preoperative Radiochemotherapy for Patients with Advanced Rectal Cancer.
Jinyoung Yoo, Ju Won Chyung, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2007;41(5):316-323.
  • 2,108 View
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AbstractAbstract PDF
BACKGROUND
An association between the epidermal growth factor receptor (EGFR) signaling pathway and the response of cancer cells to ionizing radiation has been previously described. Preoperative radiochemotherapy (PRCT) has been administered for treating locally advanced rectal cancer to improve the outcomes, and to preserve the sphincter from lowlying tumor. However, the responses of tumors to PRCT are variable and there are currently no reliable markers that predict the therapeutic benefits. We studied the association between EGFR overexpression and the tumor response to PRCT in rectal cancer.
METHODS
The EGFR protein expression, as determined by immunohistochemistry, was analyzed in the pretreatment biopsy specimens from 120 patients with advanced rectal cancer. The tumor response was graded in the surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR).
RESULTS
NR was identified in 70 cases (58.3%). Fifty patients (41.7%) responded to PRCT; 27 (22.5%) achieved a PR and 23 (19.2%) achieved a CR. EGFR overexpression was detected in 78 (65%) cases. Seventy-eight percent (39/50) of the tumors with a CR/PR revealed EGFR reactivity, whereas 55.7% (39/70) of the tumors with NR showed an EGFR expression (p=0.048).
CONCLUSIONS
The EGFR protein expression might be a valuable marker for identifying those patients who are most likely to benefit from PRCT.
K-ras Gene Mutations and Expression of K-ras, p16, Cyclin D1 and p53 in Synchronous Lesions of The Colon Adenoma-Carcinoma Sequences.
Hwa Eun Oh, Seong Jin Cho, Nam Hee Won, Dale Lee, Insun Kim, Bom Woo Yeom
Korean J Pathol. 2001;35(4):291-298.
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AbstractAbstract PDF
BACKGROUND
The colorectal adenoma-carcinoma sequence represents a well-known para-digm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence has been well investigated, the studies about tumors of different dignity co-existent in the same patient are rare. K-ras mutation is an early genetic change in colon cancer. The genes involved in the cell cycle such as cyclin D1, p16, and p53 are important in the tumorigenesis of the colon. The aims of this study were to determine K-ras gene mutation and expression of K-ras, p16, cyclin D1 and p53 in synchronous lesions of the colon adenoma-carcinoma sequences and their possible relationship with K-ras mutation.
METHODS
The materials included 45 colonic adenocarcinomas which were accompanied by adenoma (22 low grade and 26 high grade). By using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), we detected K-ras mutation of codon 12. An aberrant K-ras, p16, cyclin D1 and p53 expressions were stained using an immunohistochemical method. RESULTS: K-ras mutation was 52.4% (11/21) of high grade adenomas. K-ras expression was 65.4% (17/26) of high grade adenomas. p16 and cyclin D1 expressions were 50% (11/22) and 90.9% (20/22) of low grade adenomas, respectively. p53 expression was 75.6% (34/45) of adenocarcinomas. There were statistical correlations among K-ras, p16 and cyclin D1.
CONCLUSIONS
These results indicate that the ras gene mutation is an early event and the overexpressions of p16, cyclin D1 and p53 are associated with K-ras mutation and expression in adenoma-carcinoma sequences.
Case Report
Adenocarcinoma of the Sigmoid Colon with Prominent Rhabdoid Features: A Case Report.
Hoon Kyu Oh, Chang Ho Cho, Yoon Seup Kum
Korean J Pathol. 2008;42(1):63-65.
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AbstractAbstract PDF
Colorectal adenocarcinoma with rhabdoid features is extremely rare and only two cases have been previously reported. We report here on a case of colorectal adenocarcinoma with prominent rhabdoid features in a 69-year-old female. The specimen was an ulcerative mass from the sigmoid colon, and it measured 3.5x3 cm. Microscopic examination of the tumor showed mostly rhabdoid cells that had eccentrically located large nuclei and foci of glandular formation. A transitional area from the poorly differentiated adenocarcinoma to the rhabdoid tumor was also noted. Immunohistochemical studies showed strong reactivity of the glandular forming cells for pan-cytokeratin, and the cells were occasionally positive for vimentin. The cells with rhabdoid features were diffusely positive for vimentin and focally positive for pan-cytokeratin. These results suggested that the cells with rhabdoid features originated from dedifferentiated primary adenocarcinoma. Since colorectal adenocarcinoma with rhabdoid features is highly aggressive and unresponsive to conventional therapy, making the preoperative diagnosis is important to facilitate the treatment.
Original Articles
An Analysis of p53, bcl-2 and Ki-67 Expressions, and Apoptosis in Rectal Cancer: Their Correlation with the Tumor Response after Preoperative Radiochemotherapy.
Jinyoung Yoo, Su Zy Kim, Hyeon Min Cho, Sung Whan Kim, Hyung Min Chin, Jung Yong Lee, Jun Ki Kim, Seok Jin Kang, Chung Soo Chun, Chang Suk Kang
Korean J Pathol. 2005;39(4):222-228.
  • 2,112 View
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AbstractAbstract PDF
Background
: Preoperative radiochemotherapy (RCT) has been administered for locally advanced rectal cancer to increase the therapeutic benefits, and to preserve the sphincter in low-lying tumors, however, tumor responses after RCT are variable. Methods : Apoptotic index (AI), and expressions of Ki-67, p53 and bcl-2 were analyzed in pretreatment biopsies from 69 patients with rectal cancer by immunohistochemistry. Tumor response was graded in surgically resected specimens by using a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR). Results : CR was identified in 19 cases (28%), PR in 24 cases (35%), and NR in 26 cases (38%) of 69 cases. p53 protein was expressed in 49 cases (71%), whereas bcl-2 was in 42 cases (61%). The pretreatment Ki-67 labeling index was 65.4+/-3.4%. The tumor response was not associated with any of these markers. Tumors with CR/PR showed a higher AI (0.84+/-.84%/0.66+/-.52%) than that of tumors with NR (0.58+/-0.54%). There was a significant correlation between tumor response and the histologic differentiation (p=0.008) or recurrence (p=0.039). Conclusions : The AI revealed a tendency to increase in tumors with CR/PR, while expressions of p53 and bcl-2, and Ki-67 labeling index had little direct association with tumor response.
Expression of Cytokeratin 7 and 20 According to The Anatomical Location of Colon Cancer and The Differential Diagnosis with Cholangiocarcinoma.
Yoon Kyung Jeon, Sun Lee, Byoung Kwon Kim, Woo Ho Kim, Gyeong Hoon Kang
Korean J Pathol. 2002;36(3):146-153.
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AbstractAbstract PDF
BACKGROUND
Colonic adenocarcinoma usually shows CK7 negativity and CK20 positivity, which helps to differentiate it from cholangiocarcinoma usually showing a reverse immunohistochemical profile. We immunohistochemically investigated the pattern of CK7 and 20 expressions according to the anatomical location of colon cancer to refine the usefulness of CK expression in differential diagnosis.
METHODS
Immunohistochemical staining was done on 90 cases of surgically resected colon cancers and 84 cases of cholangiocarcinomas.
RESULTS
When the cases of colon cancer were divided into CATD (from the cecum to the descending colon) (32), sigmoid (26), and rectum (32), the positivity of CK7 was 41%, 15% and 28%, respectively, and the negativity of CK20 was 25%, 0 and 9% (p=0.013), respectively. In sigmoid colon cancers, 22 cases (85%) exhibited CK7-/CK20+ immunophenotype. However, the percentage decreased to 63% in the rectum and 47% in CATD. The CK7+/CK20- immunophenotype was found only in cancers in the cecum and ascending colon. The expression of CK7 was related to histologic differentiation (p=0.017).
CONCLUSIONS
The aberrant expressions of CKs were frequent in cancers of the rectum and ascending colon which are located in the transition site from the anus and small bowel, respectively. If adenocarcinoma in the liver were CK7+/CK20+ or CK7-/CK20-, the possibility of metastatic adenocarcinoma from CATD and rectum should be considered.
Expression of p21, p53 and Ki-67, and Apoptosis in Colorectal Adenocarcinoma.
Young Euy Park, Kyung Chan Choi, Jin Hee Sohn, Young Hee Choi, Hyung Sik Shin
Korean J Pathol. 2002;36(5):296-304.
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AbstractAbstract PDF
BACKGROUND
The purpose of this study is to assess the roles of p21 protein, p53 protein, and Ki-67 expressions and apoptosis in colorectal tumorigenesis.
METHODS
Fifty-seven colorectal cancers and 15 villotubular adenomas were investigated by immunohistochemical staining for p21 protein, p53 protein, Ki-67, and in situ labeling of apoptotic cells. Clinicopathologic values (tumor size, histologic grade, Dukes stage, and lymph node metastasis) were compared with the incidence of expressions of p21 protein and p53 protein, index of Ki-67 expression, and apoptosis.
RESULTS
The incidence of p21 protein expression was decreased with lymph node metastasis (p<0.005), and that of p53 expression was increased with lymph node metastasis (p<0.005). There were no statistically significant correlations among the p21 protein or p53 protein expressions, tumor size, histologic grade and stage. The correlation between the Ki-67 labeling index and the clinicopathologic values was not statistically significant. The labeling index of apoptosis was increased with the Astler-Coller stage (p<0.05). Statistical analysis revealed a significant inverse correlation between the p21 protein and p53 protein expressions (p<0.05).
CONCLUSIONS
It is suggested that p21 protein, p53 protein and the apoptotic labeling index are useful variables for the prognostic assessment of colorectal adenocarcinoma. Down-regulation of p21 protein expression may be associated with poor prognosis. Also, the expressions of p21 protein and p53 protein may play an important role in the tumorigenesis and progression of the colorectal adenoma-carcinoma sequence.
Case Report
Lipoma of Rectum: A Case Report.
Sung Chul Lim, Hye Keun Oh, Young Don Min
Korean J Pathol. 2002;36(5):341-343.
  • 2,536 View
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AbstractAbstract PDF
Gastrointestinal lipomas are rare and are most common in the right colon. They are in opposite distribution of predilection site in comparison to adenocarcinomas and adenomatous polyps. The peak incidence for lipoma of the large bowel is in the sixth decade when there is a high incidence of colorectal carcinoma. Because of their location and the age of the patients at presentation, large bowel lipomas are usually treated on the basis of a presumptive malignant diagnosis. A 79-year-old male is presented with a 1-year history of rectal bleeding. Colonoscopy demonstrated a pedunculated mass nearly obstructing the rectum. Anterior resection was performed. The mass consisted of submucosal lobulated mature fatty tissue with ulcerated mucosa. The authors describe a case of a submucosal lipoma of the rectum with review of literatures.
J Pathol Transl Med : Journal of Pathology and Translational Medicine
© The Korean Society of Pathologists and the Korean Society for Cytopathology.
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