title: 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.
authors.affiliation: James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Cornejo
authors.affiliation: James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA; Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA.
authors.forename: Shulin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, People's Republic of China; Department of Urology, Massachusetts General Hospital, Boston, MA.
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Urology, Guangzhou First Municipal People's Hospital, Guangzhou Medical College, Guangzhou, People's Republic of China.
authors.forename: Wei-de
authors.initials: WD
authors.lastname: Zhong
authors.affiliation: Department of Urology, Massachusetts General Hospital, Boston, MA.
authors.forename: Aria
authors.initials: A
authors.lastname: Olumi
authors.affiliation: James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Young
authors.affiliation: James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA; Department of Urology, Massachusetts General Hospital, Boston, MA. Electronic address: cwu2@partners.org.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
mesh_terms: D018249:Adenoma, Oxyphilic / Q000175:diagnosis* / Q000201:enzymology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D011379:Prognosis; D013385:Succinate Dehydrogenase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase
keywords: Clear cell; Immunohistochemistry; Oncocytoma; Prognosis; Renal cell carcinoma; Succinate dehydrogenase B
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