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Can BAP1 expression loss in mesothelial cells be an indicator of malignancy?
Hanife Gulnihal Ozdemir, Sermin Coban Kokten, Nagehan Ozdemir Barisik
J Pathol Transl Med. 2020;54(6):497-503.   Published online November 9, 2020
DOI: https://doi.org/10.4132/jptm.2020.09.14
  • 3,091 View
  • 96 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDF
Background
Malignant mesothelioma is a highly aggressive tumor that can be confused with a benign mesothelial lesion, especially cytomorphologic lesions. BRCA1-associated protein 1 (BAP1) acts as a tumor suppressor. In this study, we aim to investigate the value of BAP1 staining of malignant mesothelioma cases with expression loss and diagnosis in cell block and biopsy tissue.
Methods
Between January 2009 and March 2017, 64 mesotheliomas, 117 reactive mesothelial hyperplasias, and 20 fibrinous pleuritis/pericarditis were diagnosed with morphologic and immunohistochemical findings in our pathology clinic and were included in the study. Formalin-fixed, paraffin-embedded tissues were immunohistochemically examined for BAP1. Inflammatory and stromal cells were used as positive internal controls. BAP1 was assessed for nuclear staining in mesothelial cells.
Results
Examinations of the relationship between patient diagnosis and BAP1 biopsy status showed that the BAP1 loss rate (76.6%) was significantly higher in malignant mesothelioma cases than in other benign diseases (0%) (p<.001). Sensitivity and specificity were 76.56% and 100%, respectively, for biopsy tissue from malignant mesothelioma. Sensitivity and specificity were both 100% for BAP1 test on cell block tissue. Furthermore, the consistency between BAP1 cell block and biopsy results was excellent (ĸ=0.90) and the correlation was significant (p<.001).
Conclusions
This study shows that BAP1 expression loss in both cytology and biopsy tissue in biopsy-confirmed malignant mesothelioma cases is an essential parameter for malignant mesothelioma diagnosis.

Citations

Citations to this article as recorded by  
  • Thrombocytosis as a paraneoplastic syndrome in metastatic malignant peritoneal mesothelioma of biphasic morphology mimicking ovarian adenocarcinoma: A case report
    Moustafa S. Alhamadh, Rakan B. Alanazi, Osama Mohaamad Wadaan, Abdulrahman Yousef Alhabeeb, Mohammad Alkaiyat, Ohoud Zaid Aljarbou, Fouad Sabatin
    Clinical Case Reports.2023;[Epub]     CrossRef
  • Primary cardiac mesothelioma presenting with fulminant recurrent pericarditis: a case report
    Shmuel Schwartzenberg, Yaron Shapira, Victor Rubachevski, Ram Sharony, Harry Klimis, Domenico Filomena, Edgar Francisco Carrizales Sepulveda, Nikolaos Spinthakis, Jonathan Senior
    European Heart Journal - Case Reports.2023;[Epub]     CrossRef
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
  • 7,119 View
  • 194 Download
  • 11 Web of Science
  • 12 Crossref
AbstractAbstract PDF
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

Citations to this article as recorded by  
  • 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

J Pathol Transl Med : Journal of Pathology and Translational Medicine