Journal of Pathology and Translational Medicine

Gyeong Hoon Kang

18 Articles

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

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Abstract PDF Supplementary 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.

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

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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.

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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
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

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

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Abstract PDF Supplementary 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.

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

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Abstract 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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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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Genomic and transcriptomic characterization of heterogeneous immune subgroups of microsatellite instability-high colorectal cancers
Jung Ho Kim, Mi-Kyoung Seo, Ji Ae Lee, Seung-Yeon Yoo, Hyeon Jeong Oh, Hyundeok Kang, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang, Sangwoo Kim
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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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Abstract PDF Supplementary 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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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

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Abstract PDF Supplementary 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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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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Abstract PDF Supplementary 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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Association between the expression of epithelial–mesenchymal transition (EMT)-related markers and oncologic outcomes of colorectal cancer
Mona Hany Emile, Sameh Hany Emile, Amr Awad El-Karef, Mohamed Awad Ebrahim, Ibrahim Eldosoky Mohammed, Dina Abdallah Ibrahim
Updates in Surgery.2024; 76(6): 2181. CrossRef
TGF-β and SMAD2/4 Expression in Nonmetastatic and Metastatic Colorectal Cancer Patients
Ainul Mardiah, Hendra Susanto, Sri Rahayu Lestari, A. Taufiq, H. Susanto, H. Nur, M. Diantoro, M. Aziz, N.A.N.N. Malek
BIO Web of Conferences.2024; 117: 01001. CrossRef
Unraveling Resistance to Immunotherapy in MSI-High Colorectal Cancer
Ronald Heregger, Florian Huemer, Markus Steiner, Alejandra Gonzalez-Martinez, Richard Greil, Lukas Weiss
Cancers.2023; 15(20): 5090. CrossRef
Association of β-Catenin, APC, SMAD3/4, Tp53, and Cyclin D1 Genes in Colorectal Cancer: A Systematic Review and Meta-Analysis
Hongfeng Yan, Fuquan Jiang, Jianwu Yang, Ying-Kun Xu
Genetics Research.2022; 2022: 1. CrossRef
Comprehensive genetic features of gastric mixed adenoneuroendocrine carcinomas and pure neuroendocrine carcinomas
Jiwon Koh, Soo Kyung Nam, Yoonjin Kwak, Gilhyang Kim, Ka‐Kyung Kim, Byung‐Chul Lee, Sang‐Hoon Ahn, Do Joong Park, Hyung‐Ho Kim, Kyoung Un Park, Woo Ho Kim, Hye Seung Lee
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Menha Swellam, Entsar A. Saad, Shimaa Sabry, Adel Denewer, Camelia Abdel Malak, Amr Abouzid
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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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Abstract PDF Supplementary 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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MLH1 Methylation Status and Microsatellite Instability in Patients with Colorectal Cancer
Manuel Alejandro Rico-Méndez, Miguel Angel Trujillo-Rojas, María de la Luz Ayala-Madrigal, Jesús Arturo Hernández-Sandoval, Anahí González-Mercado, Melva Gutiérrez-Angulo, José Geovanni Romero-Quintana, Jesús Alonso Valenzuela-Pérez, Ruth Ramírez-Ramírez,
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Thai H Tran, Vinh H Nguyen, Diem TN Vo
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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
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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

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Abstract PDF Supplementary 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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Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma: Hye Eun Park, Seungyeon Yoo, Jeong Mo Bae, Seorin Jeong, Nam-Yun Cho, Gyeong Hoon Kang; J Pathol Transl Med. 2018;52(6):386-395. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.02

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Abstract PDF

Background
Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance.
Methods
Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC.
Results
SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151).
Conclusions
Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

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Reveal the Regulation Patterns of Prognosis-Related miRNAs and lncRNAs Across Solid Tumors in the Cancer Genome Atlas
Zuojing Yin, Qiming Wang, Xinmiao Yan, Lu Zhang, Kailin Tang, Zhiwei Cao, Tianyi Qiu
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Whole-Slide Image Analysis Reveals Quantitative Landscape of Tumor–Immune Microenvironment in Colorectal Cancers
Seung-Yeon Yoo, Hye Eun Park, Jung Ho Kim, Xianyu Wen, Seorin Jeong, Nam-Yun Cho, Hwang Gwan Gwon, Kwangsoo Kim, Hye Seung Lee, Seung-Yong Jeong, Kyu Joo Park, Sae-Won Han, Tae-You Kim, Jeong Mo Bae, Gyeong Hoon Kang
Clinical Cancer Research.2020; 26(4): 870. CrossRef

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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Abstract 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.

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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
Frontiers in Oncology.2024;[Epub] CrossRef
Comprehensive pan-cancer analysis reveals EPHB2 is a novel predictive biomarker for prognosis and immunotherapy response
Shengshan Xu, Youbin Zheng, Min Ye, Tao Shen, Dongxi Zhang, Zumei Li, Zhuming Lu
BMC Cancer.2024;[Epub] CrossRef
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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Hexin Lin, Lu Xia, Jiabian Lian, Yinan Chen, Yiyi Zhang, Zhicheng Zhuang, HuaJun Cai, Jun You, Guoxian Guan
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Oscar J Buckens, Btissame El Hassouni, Elisa Giovannetti, Godefridus J Peters
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Bo Jang, Hye Kim, Jeong Bae, Woo Kim, Chang Hyun, Gyeong Kang
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SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers
Bo Gun Jang, Hye Sung Kim, Jeong Mo Bae, Woo Ho Kim, Heung Up Kim, Gyeong Hoon Kang
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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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Abstract 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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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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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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Clinicopathological features and evaluation of microsatellite stability of colorectal carcinoma with cribriform comedo pattern
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Ahmed Ghdhban Al-Ziaydi
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Cribriform colon cancer: a morphological growth pattern associated with extramural venous invasion, nodal metastases and microsatellite stability
Alexander S Taylor, Natalia Liu, Jiayun M Fang, Nicole Panarelli, Lili Zhao, Jerome Cheng, Purva Gopal, Suntrea Hammer, Jing Sun, Henry Appelman, Maria Westerhoff
Journal of Clinical Pathology.2022; 75(7): 483. CrossRef
HSP110 as a Diagnostic but Not a Prognostic Biomarker in Colorectal Cancer With Microsatellite Instability
Gaelle Tachon, Arnaud Chong-Si-Tsaon, Thierry Lecomte, Audelaure Junca, Éric Frouin, Elodie Miquelestorena-Standley, Julie Godet, Camille Evrard, Violaine Randrian, Romain Chautard, Marie-Luce Auriault, Valérie Moulin, Serge Guyetant, Gaelle Fromont, Luci
Frontiers in Genetics.2022;[Epub] CrossRef
Comparative expression of immunohistochemical biomarkers in cribriform and pattern 4 non-cribriform prostatic adenocarcinoma
Guang-Qian Xiao, Elise Nguyen, Pamela D. Unger, Andy E. Sherrod
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Prognostic Predictability of American Joint Committee on Cancer 8th Staging System for Perihilar Cholangiocarcinoma: Limited Improvement Compared with the 7th Staging System
Jong Woo Lee, Jae Hoon Lee, Yejong Park, Woohyung Lee, Jaewoo Kwon, Ki Byung Song, Dae Wook Hwang, Song Cheol Kim
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Prognostic predictability of the new American Joint Committee on Cancer 8th staging system for distal bile duct cancer: limited usefulness compared with the 7th staging system
Jae Seung Kang, Seungyeoun Lee, Donghee Son, Youngmin Han, Kyung Bun Lee, Jae Ri Kim, Wooil Kwon, Sun‐Whe Kim, Jin‐Young Jang
Journal of Hepato-Biliary-Pancreatic Sciences.2018; 25(2): 124. CrossRef
Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach
Kyueng‐Whan Min, Dong‐Hoon Kim, Byoung Kwan Son, Eun‐Kyung Kim, Sang Bong Ahn, Seong Hwan Kim, Yun Ju Jo, Young Sook Park, Jinwon Seo, Young Ha Oh, Sukjoong Oh, Ho Young Kim, Mi Jung Kwon, Soo Kee Min, Hye‐Rim Park, Ji‐Young Choe, Jang Yong Jeon, Hong Il
World Journal of Surgery.2017; 41(1): 232. CrossRef
BRAF-Mutated Colorectal Cancer Exhibits Distinct Clinicopathological Features from Wild-TypeBRAF-Expressing Cancer Independent of the Microsatellite Instability Status
Min Hye Jang, Sehun Kim, Dae Yong Hwang, Wook Youn Kim, So Dug Lim, Wan Seop Kim, Tea Sook Hwang, Hye Seung Han
Journal of Korean Medical Science.2017; 32(1): 38. CrossRef
Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma
Hye Eun Park, Jung Ho Kim, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang
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Dominant high expression of wild‐type HSP110 defines a poor prognostic subgroup of colorectal carcinomas with microsatellite instability: a whole‐section immunohistochemical analysis
Hyeon Jeong Oh, Jung Ho Kim, Tae Hun Lee, Hye Eun Park, Jeong Mo Bae, Hye Seung Lee, Gyeong Hoon Kang
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Distinct features betweenMLH1-methylated and unmethylated colorectal carcinomas with the CpG island methylator phenotype: implications in the serrated neoplasia pathway
Jung Ho Kim, Jeong Mo Bae, Nam-Yun Cho, Gyeong Hoon Kang
Oncotarget.2016; 7(12): 14095. CrossRef
Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy
Lu-Ning Zhang, Wei-Wei Xiao, Shao-Yan Xi, Pu-Yun OuYang, Kai-Yun You, Zhi-Fan Zeng, Pei-Rong Ding, Hui-Zhong Zhang, Zhi-Zhong Pan, Rui-Hua Xu, Yuan-Hong Gao
Oncotarget.2016; 7(5): 6335. CrossRef

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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Abstract 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.

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Prognostic significance of microsatellite instability in colon cancer: Insights from a Propensity Score-Matched Study
Hilmi Yazici, Ayse Eren Kayaci, Melike Zeynep Can Sahin, Cisil Bayir, Aysenur Yildiz, Esin Zeynep Cinal, Muhammer Ergenc, Tevfik Kivilcim Uprak
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Unraveling the multifaceted role of EpCAM in colorectal cancer: an integrated review of its function and interplay with non-coding RNAs
Xingyu Jiang, Sumeng Wang, Qi Liang, Yiqian Liu, Lingxiang Liu
Medical Oncology.2023;[Epub] CrossRef
Outcomes of Definitive Treatment of Signet Ring Cell Carcinoma of the Rectum: Is Minimal Invasive Surgery Detrimental in Signet Ring Rectal Cancers?
S. Raghavan, Deepak Kumar Singh, J. Rohila, A. DeSouza, R. Engineer, A. Ramaswamy, V. Ostwal, A. Saklani
Indian Journal of Surgical Oncology.2020; 11(4): 597. CrossRef
Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients
Ippokratis Messaritakis, Maria Sfakianaki, Konstantinos Vogiatzoglou, Asimina Koulouridi, Chara Koutoulaki, Dimitrios Mavroudis, Maria Tzardi, Nikolaos Gouvas, John Tsiaoussis, John Souglakos
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Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis
Susu Han, Shaoqi Zong, Qi Shi, Hongjia Li, Shanshan Liu, Wei Yang, Wen Li, Fenggang Hou
EBioMedicine.2017; 20: 61. CrossRef
Prognostic factors in sporadic colon cancer with high-level microsatellite instability
Bo Young Oh, Jung Wook Huh, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Ho-Kyung Chun
Surgery.2016; 159(5): 1372. CrossRef
Clinical significance of fibroblast growth factor receptor 2 expression in patients with residual rectal cancer after preoperative chemoradiotherapy: relationship with KRAS or BRAF mutations and MSI status
Ghilsuk Yoon, Hwayoung Lee, Jae-Hoon Kim, Keun Hur, An Na Seo
Tumor Biology.2016; 37(8): 10209. CrossRef
Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis
Raj Thani Somasundaram, Jatinder Kaur, Iona Leong, Christina MacMillan, Ian J. Witterick, Paul G. Walfish, Ranju Ralhan
BMC Cancer.2016;[Epub] CrossRef
BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis
Soo Kyung Nam, Sumi Yun, Jiwon Koh, Yoonjin Kwak, An Na Seo, Kyoung Un Park, Duck-Woo Kim, Sung-Bum Kang, Woo Ho Kim, Hye Seung Lee, Wayne A Phillips
PLOS ONE.2016; 11(3): e0151865. CrossRef
Twist1-induced epithelial-mesenchymal transition according to microsatellite instability status in colon cancer cells
Bo Young Oh, So-Young Kim, Yeo Song Lee, Hye Kyung Hong, Tae Won Kim, Seok Hyung Kim, Woo Yong Lee, Yong Beom Cho
Oncotarget.2016; 7(35): 57066. CrossRef
Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma
Jung Ho Kim, Jeong Mo Bae, Young Seok Song, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang
Oncotarget.2016; 7(12): 13372. CrossRef
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
Journal of Pathology and Translational Medicine.2015; 49(2): 118. CrossRef
HER3 protein expression in relation to HER2 positivity in patients with primary colorectal cancer: clinical relevance and prognostic value
An Na Seo, Yoonjin Kwak, Woo Ho Kim, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Hye Seung Lee
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An Na Seo, Kyoung Un Park, Gheeyoung Choe, Woo Ho Kim, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
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c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer
Kyu Sang Lee, Yoonjin Kwak, Kyung Han Nam, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee, Andreas Krieg
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Nuclear Ep-ICD accumulation predicts aggressive clinical course in early stage breast cancer patients
Gunjan Srivastava, Jasmeet Assi, Lawrence Kashat, Ajay Matta, Martin Chang, Paul G Walfish, Ranju Ralhan
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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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Abstract 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.

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Diminutive and Small Colorectal Polyps: The Pathologist's Perspective
Yun Kyung Kang
Clinical Endoscopy.2014; 47(5): 404. CrossRef

CpG Island Hypermethylation in Gastric Carcinoma and Its Premalignant Lesions: Gyeong Hoon Kang; Korean J Pathol. 2012;46(1):1-9. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.1

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Abstract PDF

Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found. Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.

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