title: Immunohistochemical characterization of renal tumors in patients with Birt-Hogg-Dubé syndrome.
abstract: Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder associated with a germline mutation of folliculin (FLCN). The affected families are at a high risk for developing multiple renal cell carcinomas (RCC). Little is known about the immunostaining patterns of mutant FLCN-associated RCCs. We investigated 32 RCCs obtained from 17 BHD patients. The studied tumors included chromophobe RCCs (n = 15), hybrid oncocytic/chromophobe tumors (HOCT) (n = 14) and clear cell RCCs (n = 3). Almost all chromophobe RCCs and HOCTs revealed positive staining for S100A1, Ksp-cadherin and CD82. They stained either focally or diffusely for CK7, and were negative for CA-IX. All clear cell RCCs were positively stained for CA-IX and negative for CK7. These data confirmed that mutant FLCN-associated oncocytic and clear cell RCCs exhibited generally similar immunostaining patterns compared to their sporadic counterparts. Frequent positive staining for S100A1, Ksp-cadherin and CD82 in chromophobe RCCs and HOCTs indicated that these two types were relatively similar rather than distinctively different in their patterns of immunoreactivity. Characteristic peri-nuclear halos and polygonal cells with clear cytoplasm, which often misleads pathologists into the diagnosis of clear cell RCC, should be carefully examined using an immunohistochemical panel including CA-IX, Ksp-cadherin, CD82 and CK7.
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iribe
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yao
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Gotoda
authors.forename: Fumi
authors.initials: F
authors.lastname: Kawakami
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Imamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Midori
authors.initials: M
authors.lastname: Ando
authors.forename: Akinobu
authors.initials: A
authors.lastname: Araki
authors.forename: Jun
authors.initials: J
authors.lastname: Matsushima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Furuya
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D058249:Birt-Hogg-Dube Syndrome / Q000150:complications*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: Birt-Hogg-Dubé Syndrome (BHD); folliculin (FLCN); hybrid oncocytic/chromophobe tumor (HOCT); immunohistochemistry; renal tumor