Journal of Pathology and Translational Medicine

Original Articles

Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma: Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin; J Pathol Transl Med. 2018;52(6):378-385. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.21

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Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

Citations

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Clinical and Genomic Features of Patients with Renal Cell Carcinoma and Advanced Chronic Kidney Disease: Analysis of a Multi-Institutional Database
Corbin J. Eule, Junxiao Hu, Dale Hedges, Alkesh Jani, Thomas Pshak, Brandon J. Manley, Alejandro Sanchez, Robert Dreicer, Zin W. Myint, Yousef Zakharia, Elaine T. Lam
Cancers.2024; 16(10): 1920. CrossRef
Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma
Ziwei Gui, Juan Du, Nan Wu, Ningning Shen, Zhiqing Yang, Huijun Yang, Xuzhi Wang, Na Zhao, Zixin Zeng, Rong Wei, Wenxia Ma, Chen Wang
BMC Cancer.2023;[Epub] CrossRef
Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study
Derek H Liu, Komal A Dani, Sharath S Reddy, Xiaomeng Lei, Natalie L Demirjian, Darryl H Hwang, Bino A Varghese, Suhn Kyong Rhie, Felix Y. Yap, David I. Quinn, Imran Siddiqi, Manju Aron, Ulka Vaishampayan, Haris Zahoor, Steven Y Cen, Inderbir S Gill, Vinay
Oncology.2023; 101(6): 375. CrossRef
Immunohistochemistry for the diagnosis of renal epithelial neoplasms
Mahmut Akgul, Sean R Williamson
Seminars in Diagnostic Pathology.2022; 39(1): 1. CrossRef
BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review
Shuchi Gulati, Melissa Previtera, Primo N. Lara
Kidney Cancer.2022; 6(1): 23. CrossRef
Renal Cell Carcinoma in End-Stage Renal Disease: A Review and Update
Ziad M. El-Zaatari, Luan D. Truong
Biomedicines.2022; 10(3): 657. CrossRef
CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma
Mounika Angirekula, Sindy Y Chang, Sarah M. Jenkins, Patricia T. Greipp, William R. Sukov, Randolph S. Marks, Kenneth R. Olivier, Stephen D. Cassivi, Anja C Roden
Cancers.2022; 14(9): 2299. CrossRef
BAP1 in cancer: epigenetic stability and genome integrity
Sabrina Caporali, Alessio Butera, Ivano Amelio
Discover Oncology.2022;[Epub] CrossRef
Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell Renal Cell Carcinoma
Xiaoqin Zhang, Ziyue Wang, Zixin Zeng, Ningning Shen, Bin Wang, Yaping Zhang, Honghong Shen, Wei Lu, Rong Wei, Wenxia Ma, Chen Wang
Cancer Cell International.2021;[Epub] CrossRef
Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis
Dengyong Xu, Yuzi Xu, Yiming Lv, Fei Wu, Yunlong Liu, Ming Zhu, Dake Chen, Bingjun Bai
BioMed Research International.2020; 2020: 1. CrossRef
Functional characterisation guides classification of novel BAP1 germline variants
Jing Han Hong, Siao Ting Chong, Po-Hsien Lee, Jing Tan, Hong Lee Heng, Nur Diana Binte Ishak, Sock Hoai Chan, Bin Tean Teh, Joanne Ngeow
npj Genomic Medicine.2020;[Epub] CrossRef
Tissue-Based Immunohistochemical Markers for Diagnosis and Classification of Renal Cell Carcinoma
Liang G Qu, Vaisnavi Thirugnanasundralingam, Damien Bolton, Antonio Finelli, Nathan Lawrentschuk
Société Internationale d’Urologie Journal.2020; 1(1): 68. CrossRef
Radiogenomics: bridging imaging and genomics
Zuhir Bodalal, Stefano Trebeschi, Thi Dan Linh Nguyen-Kim, Winnie Schats, Regina Beets-Tan
Abdominal Radiology.2019; 44(6): 1960. CrossRef

The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma: Yumin Chung, Young Chan Wi, Yeseul Kim, Seong Sik Bang, Jung-Ho Yang, Kiseok Jang, Kyueng-Whan Min, Seung Sam Paik; J Pathol Transl Med. 2018;52(1):37-44. Published online October 23, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.20

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Abstract PDF Supplementary Material

Background
Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma.
Methods
Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed.
Results
Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05).
Conclusions
Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

Citations

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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;[Epub] CrossRef
The Potential Role of Genomic Signature in Stage II Relapsed Colorectal Cancer (CRC) Patients: A Mono-Institutional Study
Michela Roberto, Giulia Arrivi, Emanuela Pilozzi, Andrea Montori, Genoveffa Balducci, Paolo Mercantini, Andrea Laghi, Debora Ierinò, Martina Panebianco, Daniele Marinelli, Silverio Tomao, Paolo Marchetti, Federica Mazzuca
Cancer Management and Research.2022; Volume 14: 1353. CrossRef
Alterations of PTEN and SMAD4 methylation in diagnosis of breast cancer: implications of methyl II PCR assay
Menha Swellam, Entsar A. Saad, Shimaa Sabry, Adel Denewer, Camelia Abdel Malak, Amr Abouzid
Journal of Genetic Engineering and Biotechnology.2021; 19(1): 54. CrossRef
E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4
Chen Lu, Guangyao Ning, Panpan Si, Chunsheng Zhang, Wenjian Liu, Wei Ge, Kai Cui, Renquan Zhang, Shenglin Ge
Biochemistry and Cell Biology.2021; 99(5): 675. CrossRef
Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells
Sara Sommariva, Giacomo Caviglia, Silvia Ravera, Francesco Frassoni, Federico Benvenuto, Lorenzo Tortolina, Nicoletta Castagnino, Silvio Parodi, Michele Piana
Scientific Reports.2021;[Epub] CrossRef
Clinicopathological characterization of SMAD4-mutated intestinal adenocarcinomas: A case-control study
Xiaoyan Liao, Yansheng Hao, Xiaofei Zhang, Stephen Ward, Jane Houldsworth, Alexandros D. Polydorides, Noam Harpaz, Aldo Scarpa
PLOS ONE.2019; 14(2): e0212142. CrossRef
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
Journal of Pathology and Translational Medicine.2019; 53(5): 289. CrossRef
Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
Ion Cristóbal, Blanca Torrejón, Andrea Santos, Melani Luque, Marta Sanz-Alvarez, Federico Rojo, Jesús García-Foncillas
European Journal of Surgical Oncology.2018; 44(8): 1283. CrossRef
Reply to: Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
Jordan M. Cloyd, Takashi Mizuno, Jean-Nicolas Vauthey
European Journal of Surgical Oncology.2018; 44(8): 1285. CrossRef

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma: Kijong Yi, Hyunsung Kim, Yumin Chung, Hyein Ahn, Jongmin Sim, Young Chan Wi, Ju Yeon Pyo, Young-Soo Song, Seung Sam Paik, Young-Ha Oh; J Pathol Transl Med. 2016;50(5):327-336. Published online August 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.22

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165 Download
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Abstract PDF

Background
Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown.
Methods
Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated.
Results
E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival.
Conclusions
Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

Citations

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The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
Journal of Gastrointestinal Cancer.2024; 55(2): 599. CrossRef
Homotypic cell-in-cell structures as an adverse prognostic predictor of hepatocellular carcinoma
Ruizhi Wang, Yichao Zhu, Hao Zhong, Xinyue Gao, Qiang Sun, Meifang He
Frontiers in Oncology.2022;[Epub] CrossRef
Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes
Weronika Piorońska, Zeribe Chike Nwosu, Mei Han, Michael Büttner, Matthias Philip Ebert, Steven Dooley, Christoph Meyer
BMC Cancer.2021;[Epub] CrossRef

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