- Volume 52 Issue 6
DOI QR Code
Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma
- Wi, Young Chan (Department of Pathology, Hanyang University College of Medicine) ;
- Moon, Ahrim (Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
- Jung, Min Jung (Department of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
- Kim, Yeseul (Department of Pathology, Hanyang University College of Medicine) ;
- Bang, Seong Sik (Department of Pathology, Hanyang University College of Medicine) ;
- Jang, Kiseok (Department of Pathology, Hanyang University College of Medicine) ;
- Paik, Seung Sam (Department of Pathology, Hanyang University College of Medicine) ;
- Shin, Su-Jin (Department of Pathology, Hanyang University College of Medicine)
- Received : 2018.07.13
- Accepted : 2018.09.21
- Published : 2018.11.15
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.
Supported by : Hanyang University
- Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet 2009; 373: 1119-32. https://doi.org/10.1016/S0140-6736(09)60229-4
- Dalgliesh GL, Furge K, Greenman C, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 2010; 463: 360-3. https://doi.org/10.1038/nature08672
- Guo G, Gui Y, Gao S, et al. Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet 2011; 44: 17-9.
- Varela I, Tarpey P, Raine K, et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011; 469: 539-42. https://doi.org/10.1038/nature09639
- Hakimi AA, Ostrovnaya I, Reva B, 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: 3259-67. https://doi.org/10.1158/1078-0432.CCR-12-3886
- Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet 2012; 44: 751-9. https://doi.org/10.1038/ng.2323
- White AE, Harper JW. Cancer: emerging anatomy of the BAP1 tumor suppressor system. Science 2012; 337: 1463-4. https://doi.org/10.1126/science.1228463
- Bhattacharya S, Hanpude P, Maiti TK. Cancer associated missense mutations in BAP1 catalytic domain induce amyloidogenic aggregation: a new insight in enzymatic inactivation. Sci Rep 2015; 5: 18462.
- Murali R, Wiesner T, Scolyer RA. Tumours associated with BAP1 mutations. Pathology 2013; 45: 116-26. https://doi.org/10.1097/PAT.0b013e32835d0efb
- Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet 2016; 89: 285-94. https://doi.org/10.1111/cge.12630
- Harbour JW, Onken MD, Roberson ED, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 2010; 330: 1410-3. https://doi.org/10.1126/science.1194472
- Bott M, Brevet M, Taylor BS, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet 2011; 43: 668-72. https://doi.org/10.1038/ng.855
- Andrici J, Sheen A, Sioson L, et al. Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology. Mod Pathol 2015; 28: 1360-8. https://doi.org/10.1038/modpathol.2015.87
- Koopmans AE, Verdijk RM, Brouwer RW, et al. Clinical significance of immunohistochemistry for detection of BAP1 mutations in uveal melanoma. Mod Pathol 2014; 27: 1321-30. https://doi.org/10.1038/modpathol.2014.43
- Oka S, Inoshita N, Miura Y, et al. The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis. Urol Oncol 2018; 36: 365.e9-e14.
- Minardi D, Lucarini G, Milanese G, Montironi R, Di Primio R. Prognostic role of BAP1 in pT1 clear cell carcinoma in partial nephrectomy specimens. Virchows Arch 2017; 471: 99-105. https://doi.org/10.1007/s00428-017-2143-x
- Eble JN, Sauter G, Epstein JI, Sesterhenn IA. World Health Organization classification of tumors: pathology and genetics of tumours of the urinary system and male genital organs. Lyon: IARC Press, 2016.
- Delahunt B, Cheville JC, Martignoni G, et al. The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 2013; 37: 1490-504. https://doi.org/10.1097/PAS.0b013e318299f0fb
- Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol 2010; 34: 1233-40. https://doi.org/10.1097/PAS.0b013e3181e96f2a
- Ricketts CJ, De Cubas AA, Fan H, et al. The Cancer Genome Atlas comprehensive molecular characterization of renal cell carcinoma. Cell Rep 2018; 23: 3698.
- Kim SH, Park WS, Park EY, et al. The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: a retrospective study of tissue microarrays using immunohistochemistry. PLoS One 2017; 12: e0179610. https://doi.org/10.1371/journal.pone.0179610
- da Costa WH, da Cunha IW, Fares AF, et al. Prognostic impact of concomitant loss of PBRM1 and BAP1 protein expression in early stages of clear cell renal cell carcinoma. Urol Oncol 2018; 36: 243.e1-e8. https://doi.org/10.1016/j.urolonc.2018.01.002
- Ricketts CJ, Linehan WM. Gender specific mutation incidence and survival associations in clear cell renal cell carcinoma (CCRCC). PLoS One 2015; 10: e0140257. https://doi.org/10.1371/journal.pone.0140257
- Joseph RW, Kapur P, Serie DJ, 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: 1059-67. https://doi.org/10.1002/cncr.28521
- Kapur P, Christie A, Raman JD, et al. BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma. J Urol 2014; 191: 603-10. https://doi.org/10.1016/j.juro.2013.09.041