EXPRESSION OF BAP1 IN CLEAR CELL RENAL CELL CARCINOMA
DOI:
https://doi.org/10.55519/JAMC-02-9313Abstract
Background: BAP1 (BRCA1 associated protein 1 on chromosome 3) is a commonly mutated gene in clear cell renal cell carcinoma. Aim of the study was to evaluate the prognostic significance of BAP1 by immunohistochemistry in clear cell renal cell carcinoma. Methods: It was a descriptive case series in which data was retrospectively collected. Immunohistochemistry was used to evaluate the loss of nuclear expression of BAP1. Results: Loss of BAP1 was observed in 60% of cases of clear cell renal cell carcinoma. 27% of grade 1 tumours, 62% of grade 2 tumours, 65% of grade 3 tumours and 66% of grade 4 tumours showed loss of BAP1. Loss of BAP1 was observed in 54% cases of stage 1 tumours, 72% of stage 2 tumours and 66% of stage 3 tumours. Our study showed loss of BAP1 in 67% of cases with tumour necrosis, in 75% of cases with sarcomatoid features and in 60% of patients with distant metastasis. Conclusions: We conclude that the loss of BAP1 nuclear expression is associated with poor prognostic features. i.e., higher grade, higher stage, tumour necrosis, sarcomatoid features and distant metastasis leading to death of patients.References
Cairns P. Renal cell carcinoma. Cancer Biomark 2011;9(1-6):461–73.
Goldblum JR, Lamps LW, McKenney JK, Myers JK. Rosai and Ackerman's surgical pathology. 11th ed. Elsevier Health Sciences; 2017.
Grignon D, Che M. Clear Cell Renal Cell Carcinoma. Clin Lab Med 2005;25(2):305–16.
Mills S, Sternberg S. Sternberg's diagnostic surgical pathology. 6th ed. Philadelphia, PA: Lippincott Williams et Wilkins; 2015.
Stalhammar G. Stains & CD Markers BAP1 [Internet]. Pathologyoutlines.com. 2020 [cited 2020 Oct 6]. Available from: https://www.pathologyoutlines.com/topic/stainsBAP1.html
Jensen D, Proctor M, Marquis S, Gardner H, Ha S, Chodosh L, et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 1998;16(9):1097–112.
Harbour J, Onken M, Roberson E, Duan S, Cao L, Worley L, et al. Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas. Science 2010;330(6009):1410–3.
Testa J, Cheung M, Pei J, Below J, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet 2011;43(10):1022–5.
White A, Harper J. Emerging Anatomy of the BAP1 Tumour Suppressor System. Science 2012;337(6101):1463–4.
de la Fouchardière A, Cabaret O, Savin L, Combemale P, Schvartz H, Penet C, et al. GermlineBAP1mutations predispose also to multiple basal cell carcinomas. Clin Genet 2014;88(3):273–7.
Bretheau, D, Lechevallier E, de Fromont M, Sault MC, Rampal M, Coulange C. Prognostic value of nuclear grade of renal cell carcinoma. Cancer 1995;76(12):2543–9.
Joseph RW, Kapur P, Serie DJ, Eckel-Passow JE, Parasramka M, Ho T, et al. Erratum: Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma. Cancer 2014;120(11):1752–3.
Peña-Llopis S, Vega-Rubín-de-Celis S, Liao A, Leng N, Pavía-Jiménez A, Wang S, et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet 2012;44(7):751–9.
Gallan A, Parilla M, Segal J, Ritterhouse L, Antic T. BAP1-Mutated Clear Cell Renal Cell Carcinoma. Am J Clin Pathol 2020;155(5):718–28.
Wi Y, Moon A, Jung M, Kim Y, Bang S, Jang K, et al. Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma. J Pathol Transl Med 2018;52(6):378–85.
Hakimi A, Ostrovnaya I, Reva B, Schultz N, Chen Y, Gonen M, et al. Adverse Outcomes in Clear Cell Renal Cell Carcinoma with Mutations of 3p21 Epigenetic Regulators BAP1 and SETD2: A Report by MSKCC and the KIRC TCGA Research Network. Clin Cancer Res 2013;19(12):3259–67.
Ho T, Kapur P, Joseph R, Serie D, Eckel-Passow J, Parasramka M, et al. Loss of PBRM1 and BAP1 expression is less common in non–clear cell renal cell carcinoma than in clear cell renal cell carcinoma. Urol Oncol 2015;33(1):23.e9-23.e14.
Bihr S, Ohashi R, Moore A, Rüschoff J, Beisel C, Hermanns T, et al. Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma. Neoplasia 2019;21(2):247–56.
da Costa W, Fares A, Bezerra S, Morini M, de Toledo Benigno L, Clavijo D, et al. Loss of BAP1 expression in metastatic tumour tissue is an event of poor prognosis in patients with metastatic clear cell renal cell carcinoma. Urol Oncol 2019;37(1):78–85.
Joseph R, Kapur P, Serie D, Eckel-Passow J, Parasramka M, Ho T, et al. Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma. Cancer 2014;120(7):1059–67.
Hirosawa T, Ishida M, Ishii K, Kanehara K, Kudo K, Ohnuma S, et al. Loss of BAP1 expression is associated with genetic mutation and can predict outcomes in gallbladder cancer. PLoS One 2018;13(11):e0206643.
Eckel-Passow J, Serie D, Cheville J, Ho T, Kapur P, Brugarolas J, et al. BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumour heterogeneity and concordance with paired primary tumour. BMC Urol 2017;17(1):19.
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