title: BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma.
abstract: Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs.
authors.affiliation: From the Department of Tumor Pathology (KS, HI, HK, HS); ResearchEquipment Center (YK); Department of Surgery 1 (KF); Department ofUrology(TT, SO), Hamamatsu University School of Medicine, Hamamatsu; Department of Pathology, Fujieda Municipal General Hospital,Fujieda (KK); Division of Pathology, Seirei Mikatahara General Hospital, Hamamatsu (HO, ST); and Department of Pathology (YO); Department of Urology(TY),Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Hisaki
authors.initials: H
authors.lastname: Igarashi
authors.forename: Hisami
authors.initials: H
authors.lastname: Kato
authors.forename: Kenji
authors.initials: K
authors.lastname: Koda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Seishiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Otsuki
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Yoneda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kawanishi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Funai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takayama
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D018118:Chloride Channels / Q000096:biosynthesis*; D003937:Diagnosis, Differential; D000071837:Fibrillins; D015870:Gene Expression; D006801:Humans; D007120:Immunochemistry; D007680:Kidney Neoplasms / Q000473:pathology*; D008840:Microfilament Proteins / Q000096:biosynthesis; D017423:Sequence Analysis, RNA; D025262:Vacuolar Proton-Translocating ATPases / Q000096:biosynthesis*
chemical_list: C440005:BSND protein, human; D015415:Biomarkers; D018118:Chloride Channels; C493782:FBN3 protein, human; D000071837:Fibrillins; D008840:Microfilament Proteins; D025262:Vacuolar Proton-Translocating ATPases