Succinate dehydrogenase B: a new prognostic biomarker in clear cell renal cell carcinoma.

Abstract

Succinate dehydrogenase B (SDHB) is a mitochondrial enzyme complex subunit. Loss of SDHB protein expression has been found to correlate with SDHx gene mutations. Little is known about its expression in subtypes of renal cell carcinoma (RCC) and whether it is a prognostic indicator. Four hundred fifty renal epithelial neoplasms were analyzed for SDHB, comprising clear cell RCC (CCRCC) (n = 240), papillary RCC (n = 84), chromophobe RCC (n = 49), renal oncocytoma (n = 47), clear cell papillary RCC (CCPRCC) (n = 19), and von Hippel-Lindau (VHL)-associated CCPRCC-like tumors (n = 11). Succinate dehydrogenase B expression was graded based upon staining intensity using a 4-tiered system (0-3+), in which 3+ was strongest and complete absence was 0. Neoplasms were further categorized based upon staining extent into SDHB weak (1+-2+) and strong (3+). Succinate dehydrogenase B was strongly preserved in 131 (55%) of 240 CCRCCs, 84 (100%) of 84 papillary RCCs, 49 (100%) of 49 chromophobe RCCs, 1 (5%) of 19 CCPRCC, 5 (45%) of 11 VHL-associated CCPRCC-like tumors, and 47 (100%) of 47 renal oncocytomas. The remaining 109 CCRCCs, 18 CCPRCCs, and 6 VHL-associated CCPRCC-like tumors had weak but preserved SDHB. Succinate dehydrogenase B expression in CCRCCs with high International Society of Urological Pathology nucleolar grade (G3-G4) correlated significantly with survival (log-rank, P = .0004). Succinate dehydrogenase B is variably expressed in RCCs with clear cell morphology and strongly preserved in most other neoplasms. Therefore, weak staining, particularly in clear neoplasms, should not be misinterpreted as negative. Finally, SDHB expression in CCRCCs with high nucleolar grade (G3-G4) is significantly associated with survival, indicating it may be both a diagnostic and prognostic marker in RCC.