Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma

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.