Journal of Pathology and Translational Medicine

Original Articles

Clinicopathological implications of miR-3127 in melanoma: Truong Phan-Xuan Nguyen, Minh-Khang Le, Chau M. Bui, Vuong Gia Huy; J Pathol Transl Med. 2025;59(6):371-381. Published online October 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.08

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Abstract PDF Supplementary Material: Background
Cutaneous melanoma is the most lethal of all skin cancers. Recent studies suggested that miR-3127 is dysregulated in multiple tumor types and has important roles in tumorigenesis and cancer progression, giving it potential as a prognostic biomarker. The aim of this study was to use bioinformatic analysis to assess miR-3127 expression and correlate expression patterns with disease course in patients with cutaneous melanoma. Methods: miRNA, mRNA sequencing, DNA methylation data, and clinical information of cutaneous melanoma cases were downloaded from the Human Cancer Atlas – Skin Cutaneous Melanoma (TCGA-SKCM). miR-3127 expression was classified into miR-3127–low and miR-3127–high clusters using maximally selected rank statistics. Results: Clustering analysis showed that high expression of miR-3127 (≥20.3 reads per million) was associated with worse progression-free (p < .001) and overall (p = .011) survival compared to low miR-3127 expression. More than five thousand differentially expressed genes between the two miR-3127 sample groups encoded cell differentiation markers, cytokines, growth factors, translocated cancer genes, and oncogenes. Pathway analysis revealed that miR-3127–high samples related to activity of proliferation, DNA repair, and ultraviolet response. Conclusions: The expression level of miR-3127 could act as a prognostic indicator for patients with melanoma.

Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma: Takashi Masui, Katsunari Yane, Ichiro Ota, Kennichi Kakudo, Tomoko Wakasa, Satoru Koike, Hirotaka Kinugawa, Ryuji Yasumatsu, Tadashi Kitahara; J Pathol Transl Med. 2025;59(2):115-124. Published online February 18, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.08

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Background
We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.

Citations

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Research Progress on the Correlation between Three Biomarkers, Ki-67, CAIX and VEGF and Clear Cell Renal Cell Carcinoma
锦容马
Advances in Clinical Medicine.2025; 15(09): 326. CrossRef
Immunophenotypic Panel for Comprehensive Characterization of Aggressive Thyroid Carcinomas
Mihail Ceausu, Mihai Alin Publik, Dana Terzea, Carmen Adina Cristea, Dumitru Ioachim, Dana Manda, Sorina Schipor
Cells.2025; 14(19): 1554. CrossRef
High Ki-67 labeling index correlates with aggressive clinicopathological features in papillary thyroid carcinoma: a retrospective study
Defi Nurlia Erdian, Maria Francisca Ham, Dina Khoirunnisa, Agnes Stephanie Harahap
Thyroid Research.2025;[Epub] CrossRef

A clinicopathologic and immunohistochemical study of primary and secondary breast angiosarcoma: Evi Abada, Hyejeong Jang, Seongho Kim, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay; J Pathol Transl Med. 2022;56(6):342-353. Published online October 27, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.31

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Abstract PDF Supplementary Material

Background
We aimed to study the clinicopathologic and immunohistochemical (IHC) (CD117, c-Myc, and p53) characteristics, and overall survival of primary and secondary breast angiosarcoma (BAS).
Methods
This was a retrospective study of BAS cases diagnosed between 1997 and 2020 at our institution. Hematoxylin and eosin-stained slides were reviewed for tumor morphology, margin status, and lymph node metastasis. CD117, p53, D2-40, CD31, and c-Myc IHC stains were performed on 11 viable tissue blocks. Additional clinical information was obtained from the electronic medical records.
Results
Seventeen patients with BAS were identified. Of these, five (29%) were primary and 12 (71%) were secondary BAS, respectively. The median age at diagnosis for primary BAS was 36 years. The median age at diagnosis for secondary BAS was 67 years. The median time to secondary BAS development following radiotherapy was 6.5 years (range, 2 to 12 years). There was no significant difference between primary and secondary BAS in several histopathologic parameters examined, including histologic grade, necrosis, mitotic count, lymph node metastasis, and positive tumor margins. There was also no difference in CD117, p53, D2-40, CD31, and c-Myc expression by IHC between primary and secondary BAS. During a median followup of 21 months, primary BAS had two (40%) reported deaths and secondary BAS had three (25%) reported deaths. However, this difference in survival between both groups was not statistically significant (hazard ratio, 0.51; 95% confidence interval, 0.09 to 3.28; p = .450).
Conclusions
BAS is a rare and aggressive disease. No histologic, IHC (CD117, c-Myc, and p53), or survival differences were identified between primary and secondary BAS in this study.

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Angiosarcoma: a systematic review of biomarkers in diagnosis, prognosis, and therapeutic strategies
Huyen Thuc Tran Luong, Sofie Vercammen, Ario de Marco, Hilde de Rooster, Antonio Cosma
Frontiers in Oncology.2025;[Epub] CrossRef
Etiology, pathogenesis, and management of angiosarcoma associated with implants and foreign body: Clinical cases and research updates
Ramy Samargandi
Medicine.2024; 103(18): e37932. CrossRef
Ovarian angiosarcoma: A systematic review of literature and survival analysis
Shafi Rehman, Arya Harikrishna, Amisha Silwal, B.R. Sumie, Safdar Mohamed, Nisha Kolhe, Meghana Maddi, Linh Huynh, Jesus Gutierrez, Yoshita Rao Annepu, Ameer Mustafa Farrukh
Annals of Diagnostic Pathology.2024; 73: 152331. CrossRef
Neoadjuvant chemotherapy for radiation associated angiosarcoma (RAAS) of the breast: A retrospective single center study
Stijn J.C. van der Burg, Sophie J.M. Reijers, Anke Kuijpers, Lotte Heimans, Astrid N. Scholten, Rick L.M. Haas, Hester van Boven, Willemijn M. Kolff, Marie-Jeanne T.F.D. Vrancken Peeters, Martijn Kerst, Beatrijs A. Seinstra, Neeltje Steeghs, Winette T.A.
The Breast.2024; 78: 103825. CrossRef
Lymph node involvement in secondary breast angiosarcoma – a case presentation
Adriana Irina Ciuvică, Tiberiu Augustin Georgescu , Andrei Dennis Voichiţoiu , Angela Arsene , Luchian Marinescu , George Ionuţ Bucur , Livia Iordache , Nahedd Saba
Romanian Journal of Morphology and Embryology.2024; 65(3): 523. CrossRef
Primary ovarian angiosarcoma: Two case reports and review of literature
Ying Zhou, Yi-Wen Sun, Xiao-Yang Liu, Dan-Hua Shen
World Journal of Clinical Cases.2023; 11(21): 5122. CrossRef

Clinicopathologic features and survival outcomes of ocular melanoma: a series of 31 cases from a tertiary university hospital: Selin Kestel, Feriha Pınar Uyar Göçün, Betül Öğüt, Özlem Erdem; J Pathol Transl Med. 2022;56(4):187-198. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.10

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Abstract PDF Supplementary Material

Background
We aimed to determine the effect of clinicopathologic features on overall survival among Caucasian ocular melanoma patients in the Central Anatolia region of Turkey.
Methods
This single-center study included conjunctival (n = 12) and uveal (n = 19) melanoma patients diagnosed between January 2008 and March 2020. Clinicopathologic features and outcomes were reviewed retrospectively. Five cases were tested for BRAF V600 mutations with real-time polymerase chain reaction, and one case was tested with nextgeneration sequencing. Survival was calculated using the Kaplan-Meier method.
Results
Thirty-one patients had a mean initial age of 58.32 years (median, 61 years; range 25 to 78 years). There were 13 male and 18 female patients. The median follow-up time was 43.5 months (range, 6 to 155 months) for conjunctival melanoma and 35 months (range, 8 to 151 months) for uveal melanoma. When this study ended, eight of the 12 conjunctival melanoma patients (66.7%) and nine of the 19 uveal melanoma patients (47.4%) had died. The presence of tumor-infiltrating lymphocytes was related to improved overall survival in conjunctival melanoma (p = .014), whereas the presence of ulceration (p = .030), lymphovascular invasion (p = .051), tumor in the left eye (p = .012), tumor thickness of > 2 mm (p = .012), and mitotic count of >1/mm² (p = .012) reduced the overall survival in conjunctival melanoma. Uveal melanoma tumors with the largest diameter of 9.1–15 mm led to the lowest overall survival among subgroups (p = .035). Involvement of the conjunctiva (p=.005) and lens (p = .003) diminished overall survival in uveal melanoma. BRAF V600 mutation was present in one case of conjunctival melanoma, GNAQ R183Q mutation was present in one case of uveal melanoma. Patients with uveal melanoma presented with an advanced pathological tumor stage compared to those with conjunctival melanoma (p = .019).
Conclusions
This study confirmed the presence of tumor-infiltrating lymphocytes as a favorable factor in conjunctival melanoma and conjunctival and lens involvement as unfavorable prognostic factors in uveal melanoma for overall survival, respectively.

Citations

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Toward Precision Medicine: Gene Therapy Applications in the Management of Uveal Melanoma
Alireza Azani, Vahid Ghassemifar, Zahra Mehrdad, Maryam Saberivand, Anahid Bagheripour, Safa Tahmasebi, Hossein Gharedaghi, Malihe Sharafi, Hassan Foroozand, Mohammad Saeed Soleimani Meigoli, Saba Pourali, Arash Salmaninejad, Faeze Ahmadi Beni, Qumars Beh
Cancer Reports.2025;[Epub] CrossRef
Uveal melanoma in the Iranian population: two decades of patient management in a tertiary eye center
Hamid Riazi-Esfahani, Abdulrahim Amini, Babak Masoomian, Mehdi Yaseri, Siamak Sabour, Ali Rashidinia, Mojtaba Arjmand, Seyed Mohsen Rafizadeh, Mohammadkarim Johari, Elias Khalili Pour, Fariba Ghassemi
International Journal of Retina and Vitreous.2024;[Epub] CrossRef
Clinical features and prognosis of patients with metastatic ocular and orbital melanoma: A bi‐institutional study
Xin Liu, Han Yue, Shiyu Jiang, Lin Kong, Yu Xu, Yong Chen, Chunmeng Wang, Yan Wang, Xiaoli Zhu, Yunyi Kong, Xiaowei Zhang, Jiang Qian, Zhiguo Luo
Cancer Medicine.2023; 12(15): 16163. CrossRef
Metastatic melanoma: clinicopathologic features and overall survival comparison
Selin Kestel, Feriha Pınar Uyar Göçün, Betül Öğüt, Özlem Erdem
Acta Dermatovenerologica Alpina Pannonica et Adriatica.2022;[Epub] CrossRef

Immunohistochemical expression of programmed death-ligand 1 and CD8 in glioblastomas: Dina Mohamed El Samman, Manal Mohamed El Mahdy, Hala Sobhy Cousha, Zeinab Abd El Rahman Kamar, Khaled Abdel Karim Mohamed, Hoda Hassan Abou Gabal; J Pathol Transl Med. 2021;55(6):388-397. Published online October 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.04

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Abstract PDF

Background
Glioblastoma is the most aggressive primary malignant brain tumor in adults and is characterized by poor prognosis. Immune evasion occurs via programmed death-ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) interaction. Some malignant tumors have responded to PD-L1/PD-1 blockade treatment strategies, and PD-L1 has been described as a potential predictive biomarker. This study discussed the expression of PD-L1 and CD8 in glioblastomas.
Methods
Thirty cases of glioblastoma were stained immunohistochemically for PD-L1 and CD8, where PD-L1 expression in glioblastoma tumor tissue above 1% is considered positive and CD-8 is expressed in tumor infiltrating lymphocytes. The expression of each marker was correlated with clinicopathologic parameters. Survival analysis was conducted to correlate progression-free survival (PFS) and overall survival (OS) with PD-L1 and CD8 expression.
Results
Diffuse/fibrillary PD-L1 was expressed in all cases (mean expression, 57.6%), whereas membranous PD-L1 was expressed in six of 30 cases. CD8-positive tumor-infiltrating lymphocytes (CD8⁺ TILs) had a median expression of 10%. PD-L1 and CD8 were positively correlated (p = .001). High PD-L1 expression was associated with worse PFS and OS (p = .026 and p = .001, respectively). Correlation of CD8⁺ TILs percentage with age, sex, tumor site, laterality, and outcomes were statistically insignificant. Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis.
Conclusions
PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.

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Pathological diagnosis of central nervous system tumours in adults: what's new?
Evert-Jan Kooi, Lukas Marcelis, Pieter Wesseling
Pathology.2025; 57(2): 144. CrossRef
Expression of Programmed Cell Death-Ligand 1 (PD-L1) in Astrocytic Tumors and Its Correlation With Histopathological Grade and Proliferative Index (Ki-67): A Cross-Sectional Study
Namita Singh, Ranjana Giri, Prita Pradhan, Diptiranjan Satapathy, Ipsita Debata
Cureus.2025;[Epub] CrossRef
Immune intrinsic escape signature stratifies prognosis, characterizes the tumor immune microenvironment, and identifies tumorigenic PPP1R8 in glioblastoma multiforme patients
Ran Du, Lijun Jing, Denggang Fu
Frontiers in Immunology.2025;[Epub] CrossRef
PD-L1 Clones and Their Relevance in Glioblastoma, IDH-Wildtype: A Comparative Analysis
Michal Hendrych, Frantisek Vana, Marketa Hermanova, Radek Lakomy, Tomas Kazda, Kvetoslava Matulova, Alena Kopkova, Martina Jelinkova, Radim Jancalek, Martin Smrcka, Vaclav Vybihal, Jiri Sana
Bratislava Medical Journal.2025; 126(9): 2233. CrossRef
Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
Giuseppe Broggi, Giuseppe Angelico, Jessica Farina, Giordana Tinnirello, Valeria Barresi, Magda Zanelli, Andrea Palicelli, Francesco Certo, Giuseppe Barbagallo, Gaetano Magro, Rosario Caltabiano
Pathology - Research and Practice.2024; 254: 155144. CrossRef
Immunophenotypic Profile of Adult Glioblastoma IDH-Wildtype Microenvironment: A Cohort Study
Sofia Asioli, Lidia Gatto, Uri Vardy, Claudio Agostinelli, Vincenzo Di Nunno, Simona Righi, Alicia Tosoni, Francesca Ambrosi, Stefania Bartolini, Caterina Giannini, Enrico Franceschi
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Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report
Navid Sobhani, Victoria Bouchè, Giovanni Aldegheri, Andrea Rocca, Alberto D’Angelo, Fabiola Giudici, Cristina Bottin, Carmine Antonio Donofrio, Maurizio Pinamonti, Benvenuto Ferrari, Stefano Panni, Marika Cominetti, Jahard Aliaga, Marco Ungari, Antonio Fi
Biomedicines.2023; 11(2): 311. CrossRef
Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma
Gitanjali Sharma, Marta C. Braga, Chiara Da Pieve, Wojciech Szopa, Tatjana Starzetz, Karl H. Plate, Wojciech Kaspera, Gabriela Kramer-Marek
Cancers.2023; 15(12): 3131. CrossRef

The Prognostic Impact of Synchronous Ipsilateral Multiple Breast Cancer: Survival Outcomes according to the Eighth American Joint Committee on Cancer Staging and Molecular Subtype: Jinah Chu, Hyunsik Bae, Youjeong Seo, Soo Youn Cho, Seok-Hyung Kim, Eun Yoon Cho; J Pathol Transl Med. 2018;52(6):396-403. Published online October 23, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.03

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Abstract PDF

Background
In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer.
Methods
We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012.
Results
Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS.
Conclusions
Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1–2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

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The Role of Serum Beta-Human Chorionic Gonadotropin (β-hCG) in Differentiating Benign and Malignant Breast Lesions at a Tertiary Care Center in Jharkhand
Neyaz Ahmad, Khushboo Rani, Zenith Kerketta, Krishna Murari, Anish Baxla, Ujala Murmu, Amit Nishant, Shreya .
Cureus.2025;[Epub] CrossRef
Role of Large Format Histology in Diagnosis of Breast Carcinoma
Hari Shankar Pandey, Sanya Bhasin, Suman Kumari Pandey
NMO Journal.2025; 19(2): 189. CrossRef
Prognostic Impact of Multiple Synchronous T1 Breast Cancer
Hongki Gwak, Sung Hoo Jung, Young Jin Suh, Seok Jin Nam, Jai Hong Han, Se Jeong Oh, Eun Hwa Park, Seong Hwan Kim
Cancers.2024; 16(23): 4019. CrossRef
Deep learning-based system for automatic prediction of triple-negative breast cancer from ultrasound images
Alexandre Boulenger, Yanwen Luo, Chenhui Zhang, Chenyang Zhao, Yuanjing Gao, Mengsu Xiao, Qingli Zhu, Jie Tang
Medical & Biological Engineering & Computing.2023; 61(2): 567. CrossRef
Multicentre prospective cohort study of unmet supportive care needs among patients with breast cancer throughout their cancer treatment trajectory in Penang: a PenBCNeeds Study protocol
Noorsuzana Mohd Shariff, Nizuwan Azman, Rohayu Hami, Noor Mastura Mohd Mujar, Mohammad Farris Iman Leong Bin Abdullah
BMJ Open.2021; 11(3): e044746. CrossRef
The subgross morphology of breast carcinomas: a single-institution series of 2033 consecutive cases documented in large-format histology slides
Tibor Tot, Maria Gere, Syster Hofmeyer, Annette Bauer, Ulrika Pellas
Virchows Archiv.2020; 476(3): 373. CrossRef
Editorial for “Synchronous Breast Cancer: Phenotypic Similarities on MRI”
Uma Sharma
Journal of Magnetic Resonance Imaging.2020; 52(1): 309. CrossRef
Synchronous Multiple Breast Cancers—Do We Need to Reshape Staging?
Minodora Onisâi, Adrian Dumitru, Iuliana Iordan, Cătălin Aliuș, Oana Teodor, Adrian Alexandru, Daniela Gheorghiță, Iulian Antoniac, Adriana Nica, Alexandra-Ana Mihăilescu, Sebastian Grădinaru
Medicina.2020; 56(5): 230. CrossRef
Molecular mechanism of triple‑negative breast cancer‑associated BRCA1 and the identification of signaling pathways
Feng Qi, Wen‑Xing Qin, Yuan‑Sheng Zang
Oncology Letters.2019;[Epub] CrossRef

Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas: Alejandro España-Ferrufino, Leonardo S. Lino-Silva, Rosa A. Salcedo-Hernández; J Pathol Transl Med. 2018;52(2):79-84. Published online November 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.01

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Abstract PDF

Background
Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study.
Methods
Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group.
Results
Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023).
Conclusions
We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence.

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Investigation of Conditioned Media-Mediated Communication between Pancreatic Cancer Cells and Neurons
Didem Karakaş
Acta Medica Nicomedia.2025; 8(1): 15. CrossRef
Innervating 3D in vitro models: bioengineering and design blueprints
Mariana-Tomás de Carvalho, Margarida Henriques-Pereira, Maria V. Monteiro, Meriem Lamghari, João F. Mano, Vítor M. Gaspar
Trends in Biotechnology.2025; 43(11): 2743. CrossRef
Development and validation of a preoperative CT-based risk score integrating morphological and body composition parameters to predict recurrence-free survival in gastric cancer patients following curative surgery
Ruochen Cong, Jialei Ming, Ruonan Xu, Liyu Zhu, Xinyue Wang, Zhengqi Zhu
European Journal of Radiology.2025; 191: 112318. CrossRef
Comparison of 2D and 3D measured iodine concentration of gastric adenocarcinoma on spectral-CT and their relationship with perineural invasion
Tianxia Bei, Xiaoqiang Yao, Xuejun Chen, Yue Wu, Jing Li, Jinrong Qu
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Burak Kizil, Francesco De Virgiliis, Christoph Scheiermann
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Spectral CT-based nomogram for preoperative prediction of perineural invasion in locally advanced gastric cancer: a prospective study
Jing Li, Shuning Xu, Yi Wang, Mengjie Fang, Fei Ma, Chunmiao Xu, Hailiang Li
European Radiology.2023; 33(7): 5172. CrossRef
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Meng Huang, Gu Gong, Yicheng Deng, Xinmiao Long, Wenyong Long, Qing Liu, Wei Zhao, Rufu Chen
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Deborah A. Silverman, Vena K. Martinez, Patrick M. Dougherty, Jeffrey N. Myers, George A. Calin, Moran Amit
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Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer
Qing Tao, Wen Zhu, Xiaohui Zhao, Mei Li, Yongqian Shu, Deqiang Wang, Xiaoqin Li
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Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis
Bochao Zhao, Wu Lv, Di Mei, Rui Luo, Shiyang Bao, Baojun Huang, Jie Lin
Journal of Clinical Pathology.2020; 73(9): 544. CrossRef
Consensus-Expressed CXCL8 and MMP9 Identified by Meta-Analyzed Perineural Invasion Gene Signature in Gastric Cancer Microarray Data
Xiuzhi Jia, Minjia Lu, Chen Rui, Ying Xiao
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Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients: Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2017;51(4):388-395. Published online June 8, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.19

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods
To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results
PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions
Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

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Kota Sahara, Diamantis I. Tsilimigras, Yuki Homma, Jun Kawashima, Shishir K. Maithel, Flavio Rocha, Sharon Weber, Ryan Fields, Kamran Idrees, George A. Poultsides, Cliff Cho, Itaru Endo, Timothy M. Pawlik
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Size of Non-lepidic Invasive Pattern Predicts Recurrence in Pulmonary Mucinous Adenocarcinoma: Morphologic Analysis of 188 Resected Cases with Reappraisal of Invasion Criteria: Soohyun Hwang, Joungho Han, Misun Choi, Myung-Ju Ahn, Yong Soo Choi; J Pathol Transl Med. 2017;51(1):56-68. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.17

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Abstract PDF

Background
We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns.
Methods
Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3).
Results
The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121).
Conclusions
This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.

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Tomonari Oki, Keiju Aokage, Shogo Nomura, Kenta Tane, Tomohiro Miyoshi, Norihiko Shiiya, Kazuhito Funai, Masahiro Tsuboi, Genichiro Ishii
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Prognostic Impact of Histopathologic Features in Pulmonary Invasive Mucinous Adenocarcinomas
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Usual Interstitial Pneumonia with Lung Cancer: Clinicopathological Analysis of 43 Cases: Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Kyeongman Jeon, Man Pyo Chung, Jhingook Kim, Joungho Han; Korean J Pathol. 2014;48(1):10-16. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.10

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Abstract PDF

Background

Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.

Methods

We retrospectively reviewed the clinical and histological records of Ca patients with UIP between January 1999 and August 2013 at the Samsung Medical Center, Seoul, Korea. We found 43 patients who had Ca with UIP (UIP-Ca). Previously reported data of eighty-four patients with UIP-only were included as a comparison group.

Results

Smoking is related to poor prognosis in patients with UIP-Ca, and the number of patients with a high smoking index of more than 30 pack-years significantly increased in UIP-Ca patients compared with UIP-only patients. There is no significant prognostic differentiation between UIP-Ca patients and UIP-only patients. Microscopically, UIP-Ca patients showed characteristically heterogeneous histological patterns and degrees of differentiation. There were many foci of squamous metaplasia or dysplasia at the peripheral area of squamous cell carcinomas.

Conclusions

We report 43 cases of UIP-Ca. Our results suggest that smoking is related to cancer occurrence in UIP patients and poor prognosis in UIP-Ca patients.

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Usual Interstitial Pneumonia and Lung Cancer
Lamiyae Senhaji, Meryem Karhate, Abir Bouhamdi, Mounia Serraj, Mohamed ElBiaze, Mohammed Chakib Benjelloun, Badreddine Alami, Bouchra Amara
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Yet H. Khor, Yvonne Ng, Hayley Barnes, Nicole S.L. Goh, Christine F. McDonald, Anne E. Holland
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Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – analysis of institutional and population data
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Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma: Jiyeon Hyeon, Soomin Ahn, Jae Jun Lee, Dae Hyun Song, Cheol-Keun Park; Korean J Pathol. 2013;47(2):130-136. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.130

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Abstract PDF

Background

BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients.

Methods

We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months.

Results

Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078).

Conclusions

BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.

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Yupeng Nie, Rixu Liu, Haoyang Sun, Yongchang Yao
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The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities
Minjie Wu, Heng Dong, Chao Xu, Mengqing Sun, Haojin Gao, Fangtian Bu, Jianxiang Chen
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The role of BCL9 genetic variation as a biomarker for hepatitis C-related hepatocellular carcinoma in Egyptian patients
Eman Abd El Razek Abbas, Ahmed Barakat Barakat, Mohamed Hassany, Samar Samir Youssef
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Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma
Kwang-Hoon Chun
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Wnt/β-Catenin Signalling and Its Cofactor BCL9L Have an Oncogenic Effect in Bladder Cancer Cells
Roland Kotolloshi, Mieczyslaw Gajda, Marc-Oliver Grimm, Daniel Steinbach
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Zhuang Wei, Mei Feng, Zhongen Wu, Shuru Shen, Di Zhu
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Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma
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Hypoxia activates Wnt/β-catenin signaling by regulating the expression of BCL9 in human hepatocellular carcinoma
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CHD1L Is a Marker for Poor Prognosis of Hepatocellular Carcinoma after Surgical Resection: Jiyeon Hyeon, Soomin Ahn, Cheol-Keun Park; Korean J Pathol. 2013;47(1):9-15. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.9

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Abstract PDF

Background

The gene for chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC.

Methods

We investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months.

Results

CHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher α-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival.

Conclusions

CHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.

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Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes: Joo-Yeun Kim, Na Ri Shin, Ahrong Kim, Hyun-Jeong Lee, Won-young Park, Jee-Yeon Kim, Chang-Hun Lee, Gi-Young Huh, Do Youn Park; Korean J Pathol. 2013;47(1):28-35. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.28

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Abstract PDF

Background

Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear.

Methods

MSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed.

Results

Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197).

Conclusions

Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.

Citations

Citations to this article as recorded by

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Expression of Multidrug Resistance Protein 1 in Human Hepatocellular Carcinoma.: Yun Kyung Kang; Korean J Pathol. 2011;45(3):281-289.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.281

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Abstract PDF

BACKGROUND
Multidrug resistance protein 1 (MDR1) encoded by ATP-binding cassette, sub-family B (Mdr/Tap), member 1 (ABCB1) mediates cross-resistance to antineoplastic drugs, and its expression is related to tumor aggressiveness.
METHODS
MDR1 expression was investigated in 100 hepatocellular carcinomas (HCCs) by immunohistochemical staining. The epigenetic mechanisms underlying ABCB1 transcriptional regulation were investigated in cell lines.
RESULTS
MDR1 was normally localized in the bile canalicular surface of the hepatocytes. Among 100 HCCs, 45 showed canalicular/luminal (CL) staining similar to the normal pattern, another 45 displayed membranous/cytoplasmic (MC) overexpression, and the remaining 10 revealed loss of expression. MC pattern or null staining of HCCs correlated with a higher histological grade and had a poorer prognosis than HCCs with a CL pattern (p<0.05). They also tended to have a poor prognosis by multivariate survival analysis. The ABCB1 promoter was hypomethylated regardless of MDR1 expression or ABCB1 mRNA levels in 10 HCC cell lines. Histone deacetylase inhibitor treatment induced ABCB1 upregulation in 4 cell lines with low or moderate ABCB1 levels.
CONCLUSIONS
Our findings suggest that either an increase or a loss of MDR1 expression may contribute to the poor outcome of HCCs; histone deacetylation may be one of the epigenetic mechanisms directing the ABCB1 expression in HCCs.

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Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials
Safaa MM Abd El Khalek, Mona QR Mohammed, Amira M Al Balakosy
Egyptian Journal of Pathology.2023; 43(1): 66. CrossRef

Prognostic Implications of the Expression of CXCL16 in Breast Carcinoma.: Dong Youl Choi, Ran Hong, Sung Churl Lim, Keun Hong Kee, Chae Hong Suh, Mija Lee; Korean J Pathol. 2011;45(1):15-20.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.15

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Abstract PDF

BACKGROUND
Of the many prognostic factors for breast cancer, the relationship between an infiltration of inflammatory cells and the prognosis is debatable. Of the chemokines affecting cancer's inflammatory reactions, chemokine (C-X-C motif) ligand 16 (CXCL16) has attracted attention for its prognostic value in many cancers, including colorectal cancer and renal cell carcinoma. But the situation for breast carcinoma is unknown. The aim of this study was to examine the relationship between the prognostic factors and the CXCL16 expression in patients with breast carcinoma.
METHODS
The patients (n=106) diagnosed with invasive ductal cancer of the breast were enrolled. We reviewed the clinicopathological factors of these patients, hematoxylin and eosin stains were prepared and estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2/neu) and CXCL16 immunostaining was performed.
RESULTS
The ER expression was significantly correlated with age and inflammation. A CXCL16 expression was noted in 81.1% of the cases. No association was evident between a CXCL16 expression and any other parameter, including the survival rate. Multivariate analysis did not implicate ER, HER2/neu or CXCL16 as an independent prognostic factor, but the tumor size was independent predictive factor for the patient outcome.
CONCLUSIONS
An inflammatory reaction mediated by CXCL16 is not associated with the prognosis of breast cancer or any clinicopathological factors.

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The Emerging Role of CXC Chemokines And Their Receptors in Cancer
Victoria Vinader, Kamyar Afarinkia
Future Medicinal Chemistry.2012; 4(7): 853. CrossRef

A Pathologic Study of Renal Cell Carcinoma: Correlation between clinical and morphologic parameters and prognosis.: Hye Seon Ahn, Moon Hyang Park; Korean J Pathol. 1992;26(6):561-572.

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Abstract PDF: The prognostic significance of morphologic parameters was evaluated in 36 cases of renal cell carcinoma diagnosed during five years(1986~1990). We reviewed and classified on the basis of pathologic stage, tumor size, histologic pattern, cell type and nuclear grade. Mean age was 51 years old. Average tumor size was 7.3 cm in diameter. Six of 35 patients died of disease. Overall mean survival was 43.3+/-7.3 months. An increasing nuclear grade was generally correlated with a decrease in cummlative survival rate. Similarly, a higher stage at the time of diagnosis could predicated a low survival rate only for high nuclear grade carcinoma. There was an apparent positive correlation between grade and age, grade and size, grade and cell type, cell type and histologic pattern as well as stage and age. This positive correlations are in part a function of nuclear grade; only 20% of grade 3 & 4 tumor consisted of clear cells whereass 71% of grade 1 & 2 consisted of clear cell type. All 6 cases of granular cell types and 50% of mixed cell type were grade 3 & 4. The tumor size of the primary was well correlated with the nuclear grade. Nuclear grade was the most significant factor among the morphologic parameters studied.

Prognostic Significance of Thymosin- 4 in Gastric Adenocarcinoma Patients.: Lucia Kim, Ye Ji Kim, Suk Jin Choi, In Suh Park, Jee Young Han, Young Chae Chu, Joon Mee Kim; Korean J Pathol. 2007;41(3):176-182.

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Abstract PDF: Background
: Thymosin- 4 is an actin-sequestering protein that regulates actin polymerization. It is known to be associated with cell migration, angiogenesis and wound healing, as well as with tumor metastasis.
Methods
: We immunohistochemically evaluated the thymosin- 4 expression in gastric adenocarcinoma specimens, the relationship between this protein and the pathologic features and other tumor-related proteins, and its influence on the patient outcome.
Results
: We demonstrated that 40 specimens (26.3%) of 152 gastric adenocarcinomas showed positivity for thymosin- 4. The thymosin- 4 expression was statistically associated with advanced tumor stage (p=0.010), the nodal stage (p=0.029), the TNM stage (p=0.008), and the presence of lymphovascular invasion (p=0.009). The thymosin- 4 protein expression was closely related to the positivity for VEGF (p=0.000), c-Myc (p=0.007), and cyclin D1 (p=0.005), but it was not associated with the E-cadherin (p=0.861) or -catenin (p=0.640) expressions. The median survival and disease relapse time of patients showing thymosin-4 immunoreactivity were statistically shorter than those of patients without expression. Multivariate analysis showed that the tumor stage (p=0.003), nodal stage (p=0.005), thymosin- 4 expression (p=0.019) and Lauren's classification (p=0.037) were statistically important prognostic factors for gastric adenocarcinomas.
Conclusions
: The thymosin- 4 expression might be associated with disease progression of gastric adenocarcinomas and it should be regarded as an important prognostic factor for estimating patient survival.

Case Report

A Case of Intestinal Anthrax with Recovery after Surgical Intervention .: Jong Im Lee, Jung Ran Kim, Dong Hoon Kim, Byoung Ook Jeoung; Korean J Pathol. 1995;29(2):268-271.

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Abstract PDF: Anthrax in man is usually cutaneous, resulting from contact with materials derived from infected livestock. Internal organs are infrequently involved,. This report concerns a case of primary anthrax of intestine. The first case of primary anthrax of intestine is to our knowledge in Korea. The patient was a 14-year-old male who has complained of nausea, vomiting and acute abdominal pain. History was otherwise noncontributory except for ingestion raw meat of the dead cattle, one day before the onset of the disease. The cattle presumably died due to Bacillus anthracis in a village Bae-Ban Dong in the city of Kyung ju, Kyung Pook. Among 15 sufferers, 2 cases died 3 days later. Bacillus anthracis isolated from the raw beef, blood samples of two patients and throat culture of one patient. At laparotomy, the peritoneal cavity was full of serosanginous fluid. Right hemicolectomy including partial resection of ileum was done. The bowel was segmentally dilated, hemorrhagic and necrotic, especially at terminal ileum. The mucosa was edematous and largely ulcerated covered with greenish yellow exudate. The intense vascular congestion with hemorrhage and numerous colonization of bacteria were present through the entire wall. The organisms were large, gram-positive and PAS-negative bacilli in long chain. Bacterial emboli were scattered in lymphatics. The other feature was band like lymphoid cell infiltration in ulcer base and submucosal layer. Payer's patches were prominent and the germinal centers were necrotic. Interfollicular spaces exhibited aggregates of numerous atypical lymphoid cells. The cells were five times larger than resting lymphocytes and had several prominent nucleoli and abundant amphophilic cytoplasm. On immunohistochemical staining, most of atypical cells were positive for T-cell marker and Ki-I Ag. The mesenteric lymph nodes were enlarged, showing reactive feature, and the atypical cells were also demonstrated. The patient recovered completely.

Original Articles

Clinicopathologic Significance of CD44s, CD44v5 and CD44v6 Expression in Non Small Cell Lung Carcinomas.: Jae Kyun Kim, Chang Hun Lee, Kyeong Min Lee, Jin Mi Song; Korean J Pathol. 2004;38(2):93-99.

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Abstract PDF: BACKGROUND
CD44 is a polymorphic family of transmembrane glycoproteins generated by alternative splicing of messenger RNA and is involved in the mechanism of tumor invasion and metastasis.
METHODS
The expression of selected CD44 molecules (CD44s, CD44v5, and CD44v6) was determined immunohistochemically in 84 cases of non small cell lung carcinomas (NSCLCs). The results were compared with PCNA index, microvessel density (MVD), and clinicopathological parameters including patient? survival.
RESULTS
CD44s showed a positive reaction in 61.9% (52/84) of NSCLCs, CD44v5 in 73.8% (62/84), and CD44v6 in 39.3% (33/84). Squamous cell carcinomas (SCCs) displayed preferential expression of all CD44 molecules in comparison with adenocarcinomas (ACs) (p<0.001). As a whole, the expression of CD44 molecules was not correlated with clinical parameters (stage, TNM-T, and TNM-N), PCNA index, or MVD. For ACs only, however, CD44v5 expression was negatively correlated with PCNA index (p<0.05). Poor survival was correlated with CD44v5 expression in ACs and CD44v6 in SCCs (both, p<0.05).
CONCLUSIONS
These findings suggest that CD44 molecule in NSCLC could be a distinctive phenotypic marker for SCC, and the possibility that CD44v5 and CD44v6 are in some way instrumental in conditioning the biologic behavior of NSCLC according to major histologic types.

Twist Expression in Upper Urinary Tract Urothelial Carcinoma Affects Patients Disease Free Survival and is Associated with Tumor Grade.: Dong Il Kim, Sun Och Yoon, Seog Yun Park, Bomi Kim, Gyeong Hoon Kang, Kyung Chul Moon; Korean J Pathol. 2007;41(5):324-328.

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Abstract PDF: BACKGROUND
Epithelial-mesenchymal transition (EMT) is critical for morphogenesis during embryonic development and is also implicated in the conversion of early-stage tumors into invasive malignancies. Recently, Twist has been identified to play an important role in EMTmediated metastatic progression of several types of human cancer. The present study examined the expression of Twist and evaluated its clinicopathologic significance in urothelial carcinoma of upper urinary tract.
METHODS
Immunohistochemical staining for Twist expression was performed on 70 upper urinary tract urothelial carcinomas (UUT-UCs) using tissue microarray.
RESULTS
Immunohistochemical staining for Twist was positive in 31/70 cases (44.3%) of UUT-UCs. Twist expression was associated with high-grade and advanced-stage (ISUP grade, p<0.01; stage, p=0.045). The patients with Twist positive-tumors revealed lower disease free survival rate than those with Twist negative-tumors (p<0.01). The overall survival for patients with Twist positive-tumors was slightly worse than the patients with Twist negative- tumors, but the difference was not statistically significant (p=0.12).
CONCLUSION
Our results suggest that Twist is a novel marker for advanced UUT-UC.

Expressions of the Tumor Associated Proteins and Their Correlation with the Pathologic Features in Childhood Hepatoblastoma.: Han Seong Kim, Hyo Seop Ahn, Kwi Won Park, Ja June Jang; Korean J Pathol. 1997;31(6):538-545.

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Abstract PDF: Hepatoblastoma is a rare malignant liver tumor found in children. Its biological characteristics and prognostic factors have not been well known. We investigated 29 cases of hepatoblastoma, registered in university hospitals in Seoul from 1984 to 1996. By the immunohistochemical method, p53, Waf-1 (p21), bcl-2, heat shock protein 70 (hsp70), c-jun, transforming growth factor-alpha (TGF-alpha) expressions were studied. Those data were compared with clinico-pathologic features; age, sex, tumor size, tumor stage and histologic subtypes. Expression of p53 and bcl-2 were each observed separately in single cases. Expression of c-jun was more frequently noted in patients at higher stages. Expression of TGF-alpha decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Cumulative survival rate was lower in females than in males and in patients with a higher tumor stage. According to histologic subtypes, survival rates decreased in the order of pure fetal, mixed, embryonal and small cell anaplastic subtypes. Survival rate was lower in patients with c-jun expression. Group of TGF-alpha labelling index under 19 showed a lower survival rate than that over 19. In conclusion, we found that tumor associated proteins, c-jun and TGF-alpha, are closely related to the prognosis of hepatoblastoma but p53 and bcl-2 may not be related to it.

Prognostic Significance of Abnormal beta - catenin Expression in Breast Carcinoma.: Won Ae Lee; Korean J Pathol. 2005;39(2):114-119.

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Abstract PDF: BACKGROUND
The subcellular localization and activity of beta-catenin are tightly regulated within the cell. The aim of this study was to analyze the aberrant beta-catenin expression in breast carcinomas and to determine its clinical significance.
METHODS
Fifty five cases of breast carcinoma were immunostained with monoclonal antibodies against beta-catenin. Normal expression of -catenin was defined as exclusive membranous staining. Abnormal expression of beta-catenin was reclassified into 3 categories: complete or partial loss of membranous staining (LOM) without cytoplasmic staining and nuclear staining, LOM with cytoplasmic staining and without nuclear staining, and LOM with nuclear staining and with/without cytoplasmic staining. RESULTS: Normal membranous beta-catenin expression was detected in 25 (45.5%) of 55 cases of breast carcinoma. Thirty cases with abnormal -catenin expression comprised 9 cases (16.1%) showing LOM without cytoplasmic and/or nuclear staining, 20 cases (36.4%) showing LOM with cytoplasmic staining and without nuclear staining, and one case (1.8%) showing LOM with nuclear and cytoplasmic staining. Abnormal beta-catenin expression was significantly correlated with lymph node metastasis (p=0.03). LOM with cytoplasmic and/or nuclear expression was significantly correlated with poor disease free survival by univariate (p=0.03) and multivariate analyses (p=0.03). In addition, it was correlated with poor overall survival with a borderline significance (p=0.059).
CONCLUSIONS
This study suggests that the cytoplasmic and/or nuclear expression of beta-catenin can be used as a biologic marker for predicting disease recurrence and poor patients' survival in breast carcinomas.

Correlation of Expression of CD44, p53 and bcl-2 Protein, DNA Ploidy Pattern, and Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.: Mi Ja Lee, Ho Jong Jeon, Kweon Cheon Kim; Korean J Pathol. 1999;33(12):1152-1162.

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Abstract PDF: In this study of 64 cases of breast cancer with a clinical follow-up period of more than 5 years, several prognostic factors were evaluated. The purpose of this study was to determine whether any one parameter or group of parameters serves as adequate predictors of tumor behavior and patient's prognosis. Several prognostic factors included clinicopathological variables (patient's age, histologic grade, status of lymph node (LN) metastasis, and tumor size), expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2 and CD44 by immunohistochemistry, and DNA ploidy pattern. The results showed that the expression of ER and PR had a significant inverse correlation with the histologic grade (ER, p=0.05; PR, p<0.05). The expression of p53 protein showed a significant relationship with high histologic grade of tumor (p<0.05). The expression of bcl-2 protein was preferably seen in low histologic grade of tumor (p<0.05) and significantly associated with ER positive or PR positive tumors (ER, p<0.05; PR, p<0.05). This results suggest that bcl-2 protein might play significant roles in ER and PR. The CD44 expression showed a significant relationship with tumor size (p<0.05). The large size and aneuploidy pattern of tumor had a tendency to be associated with shorter patient survival. Cox's multivariate analysis showed that overall survival was affected by LN metastasis because of the shorter survival in patients with LN metastasis. In conclusion, tumor size, DNA ploidy pattern, and LN metastasis were themselves significant predictors of breast cancer survival rate.

The Loss of Expression of Caveolin-1 in Gastrointestinal Stromal Tumors.: Eo Jin Kim, Jin Hee Sohn, Min Kyung Kim, Seoung Wan Chae, Hye Seung Lee, Eun Yoon Cho, Woo Ho Kim; Korean J Pathol. 2005;39(5):338-344.

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Abstract PDF: BACKGROUND
The down-regulation of caveolin-1, a putative tumor suppressor gene, has been demonstrated in several types of sarcomas. However, it's not known whether or not the gastrointestinal stromal tumors (GISTs) express caveolin-1. We carried out this study to investigate the caveolin-1 expression in GISTs and to determine the correlation between the clinicopathologic profiles of GISTs and the expression of caveolin-1.
METHODS
One hundred eight cases of formalin-fixed and paraffin-embedded tissues of GISTs were immunohistochemically evaluated for the expression of caveolin-1 by using the tissue-array method. Survival data of 98 cases of primary GISTs was analysed according to the expression status of caveolin-1.
RESULTS
Ninety three cases (86.1%) of 108 GISTs did not express caveolin-1 protein. There was no correlation between the caveolin-1 expression status and any of the clinicopathologic variables, including mitosis (p=0.948) and tumor grade (p=0.334). The expression of caveolin-1 was not correlated with other immunohistochemical marker proteins including, c-kit (p=0.373), CD34 (p=0.437) and SMA (p=0.831). On the univariate analysis, the caveolin-1 expression status (p=0.635) was not a significant predictor of the disease-free survival for GIST patients.
CONCLUSIONS
The results of this study suggest that caveolin-1 might act as a tumor suppressor gene in the GIST oncogenesis, but it has no function as a prognostic marker for disease free survival.

Significance of Expression of p16, Cyclin D1, Rb, and p53 Protein and Correlation with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.: Mi Ja Lee, Ho Jong Jeon, Kweon Cheon Kim; Korean J Pathol. 2000;34(4):288-299.

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Abstract PDF: The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle regulation. Perturbations in this pathway due to a variety of genetic aberrations have been reported in many human cancers including breast cancer. We examined the significance of immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER), and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between p16 and pRb expression. There was no correlation between p16 staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grade, higher ER and PR expression. The expression of p53 protein showed a significant correlation with high tumor grade. In a Cox multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor size and lymph node status were independent predictors of patient outcome.

Correlations between the Expression of c-Abl, c-Kit, Platelet-derived Growth Factor Receptor (PDGFR)-alpha and PDGFR-beta and Survival in Patients with Ovarian Cancer.: Heejeong Lee, Keun Ho Lee, Kyo young Lee, Chang Suk Kang; Korean J Pathol. 2006;40(3):210-216.

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Abstract PDF: BACKGROUND
:Protein tyrosine kinases (PTKs) such as c-Abl, c-KIT, PDGFR-alpha and PDGFR-bata are key proteins in the regulation of cell growth. In this study, we evaluated the correlations between the expression of c-Abl, c-KIT, PDGFR-alpha and PDGFR-beta and the survival of patients with ovarian cancer.
METHODS
We performed the immunohistochemistry for 102 patients with ovarian cancer and we retrospectively reviewed the overall and disease free survival and also the response to platinum-based chemotherapy in those patients.
RESULTS
The short disease free survival rate was significantly associated with the increased expression of PDGFR-alpha (p=0.0459). The short overall survival time in patients with advanced (stage III and IV) ovarian cancer was associated with the overexpression of c-Abl (p=0.0268) and the reduced expression of c-KIT (p=0.0307). On multivariate analysis, the tumor stage and c-Abl maintained their prognostic influence. Meanwhile, none of the four PTK expression patterns predicted the response to the platinum-based chemotherapy.
CONCLUSIONS
Our data suggest that for patients with advanced ovarian cancer, the overexpression of c-Abl and the reduced expression of c-KIT might be used as poor prognostic factors for overall survival. It is further noteworthy that the tumor stage and c-Abl may be useful in predicting the patients' survival. Although any of the four PTKs could not predict the response to platinum chemotherapy, the expression of the kinases targeted by tyrosine kinase inhibitor suggests the potential usefulness of imatinib mesylate for the treatment of ovarian cancer.

Prognostic Significance of PCNA Index and AgNORs Score in Transitional Cell Carcinoma of the Renal Pelvis.: Wan Seop Kim, Seung Sam Paik, Nam Hoon Kim, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1998;32(7):521-530.

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Abstract: Proliferative activity of a malignant tumor is known to reflect its biological aggressiveness. Proliferating cell nuclear antigen (PCNA) is a marker of cellular proliferation, and silver-stained nucleolar organizer regions (AgNORs) have been shown to correlate with ploidy and proliferative activity of cells. In transitional cell carcinoma of the renal pelvis, the prognostic value of these markers has not been well defined. We studied PCNA expression and the AgNORs count in 22 transitional cell carcinoma of the renal pelvis to assess their prognostic significance compared with their cumulative survival rate, the stage of disease and histopathologic features of the tumors. An immunohistochemical method and a standard colloidal silver staining were used. The mean percentage of PCNA positivity (PCNA index) and the mean number of AgNORs per nucleus (AgNORs score) were determined. In a multivariable analysis, PCNA indexes were significantly associated with tumor stage (p=0.024), whereas AgNORs scores were not significantly associated with the stage or histopatholgic features of the tumors. Histologic grade was correlated to disease stage at a significant level (p=0.000). But there was a trend of low tumor PCNA-indices or AgNORs counts with survival advantage for patients, but this did not reach statistical significance. The results suggest that the fraction of PCNA positive nuclei would be useful for investigating the malignant potential of renal pelvic cancers, although their clinical use as markers of biologic behavior may be limited.

Prognostic Implications of Ki-67 Labelling Index and p53, bcl-2 Protein Expression in the Primary Central Nervous System Lymphoma.: Jae Ho Han, Woo Ick Yang, Tai Seung Kim; Korean J Pathol. 2000;34(6):456-464.

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Abstract PDF: It has been claimed that CNS lymphoma, a rare neoplasm accounting for only a small fraction of malignant brain tumors, occurs with increasing frequency in immunologically normal as well as immunocompromised individuals. We investigated the prognostic value of Ki-67 index, p53, and bcl-2 oncoprotein expression in relation to the clinicopathological parameters in the primary CNS lymphoma patients. The tumors were graded by Kiel classification and the Working formulation and included 33 high-grade, 4 intermediate-grade, and 5 low-grade lymphomas. The phenotype was determined in 38 cases: 30 were B cell type and 8 were T cell type. All cases displayed variable degrees of nuclear Ki-67 staining from 1.0% to 92.0% (mean 51.1%). A highly significant correlation was established between the proportion of Ki-67 positive cells and the classification into grades (p=0.0002) and phenotypes (p=0.0002). Overexpression of p53 and bcl-2 protein was found in 37.1% and 51.4% of 35 patients, respectively. And p53 expression was significantly increased in B cell type (p=0.02). On Kaplan-Meier survival curve, the phenotype, grade of tumors, and p53 and bcl-2 protein expression were not correlated with overall survival. On multivariate analyses, overall survival was independently influenced by Ki-67 index. In conclusion, it is suggested that Ki-67 proliferating index is the most important marker for predicting biologic behavior of the primary CNS lymphoma.

Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.: Yoon Jung Choi, Woo Hee Jung, Hy De Lee, Kwang Gil Lee; Korean J Pathol. 2000;34(9):652-664.

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Abstract PDF: Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.

Significance of Circumferential Resection Margin Involvement Following Esophagectomy for Esophageal Cancer.: Mee Sook Roh, Jae Ik Lee, Phil Jo Choi; Korean J Pathol. 2004;38(1):23-28.

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Abstract PDF: BACKGROUND
This study was performed to examine the significance of the circumferential resection margin (CRM) involvement by a tumor on the postoperative survival after esophageal cancer surgery.
METHODS
Fifty nine resected cases of esophageal cancers were retrospectively reviewed. The presence of a tumor either at, or within 1 mm of, the CRM was recorded. By an immunohistochemical study for Ki-67, the Ki-67 differential grades (Ki-67 DG) were defined according to the differences between the Ki-67 labeling indices of the central and of peripheral areas of the tumor nearest to the CRM: Ki-67 DG 0 (< or =10%) and Ki-67 DG 1 (>10%). The CRM involvement was correlated with the clinicopathological factors, Ki-67 DG and survival data.
RESULTS
CRM involvement was found in 26 (44.1%) of the 59 cases. There were significant differences in the cases, both with and without CRM involvement of tumor cells, in relation to lymph node metastasis, lymphovascular, perineural invasions and tumor stage (p<0.05). Ten (38.3%) of the 26 with, and 3 (9.1%) of 33 cases without, CRM involvement, showed Ki-67 DG 1 (p=0.007). The 3-year survivals of patients with and without CRM involvement were 26.8 and 61.8%, respectively (p=0.003).
CONCLUSIONS
These results show that the CRM involvement status may be used as a predictor of survival after esophageal cancer surgery, and CRM involvement is more an indicator of an advanced disease than of an incomplete resection.

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