Open AccessDistinctive expression patterns of glycoprotein non‐metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome
Author(s) -
Furuya Mitsuko,
Hong SeungBeom,
Tanaka Reiko,
Kuroda Naoto,
Nagashima Yoji,
Nagahama Kiyotaka,
Suyama Takahito,
Yao Masahiro,
Nakatani Yukio
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12601
Subject(s) - folliculin , chromophobe cell , birt–hogg–dubé syndrome , loss of heterozygosity , renal cell carcinoma , pathology , immunohistochemistry , germline mutation , medicine , cancer research , biology , cancer , mutation , clear cell , gene , genetics , pneumothorax , allele , radiology
Birt–Hogg–Dubé syndrome ( BHD ) is an inherited disorder associated with a germline mutation of the folliculin gene ( FLCN ). The affected families have a high risk for developing multiple renal cell carcinomas ( RCC ). Diagnostic markers that distinguish between FLCN ‐related RCC and sporadic RCC have not been investigated, and many patients with undiagnosed BHD fail to receive proper medical care. We investigated the histopathology of 27 RCC s obtained from 18 BHD patients who were diagnosed by genetic testing. Possible somatic mutations of RCC lesions were investigated by DNA sequencing. Western blotting and immunohistochemical staining were used to compare the expression levels of FLCN and glycoprotein non‐metastatic B ( GPNMB ) between FLCN ‐related RCC s and sporadic renal tumors ( n = 62). The expression of GPNMB was also evaluated by quantitative RT ‐ PCR . Histopathological analysis revealed that the most frequent histological type was chromophobe RCC ( n = 12), followed by hybrid oncocytic/chromophobe tumor ( n = 6). Somatic mutation analysis revealed small intragenic mutations in six cases and loss of heterozygosity in two cases. Western blot and immunostaining analyses revealed that FLCN ‐related RCC s showed overexpression of GPNMB and underexpression of FLCN , whereas sporadic tumors showed inverted patterns. GPNMB mRNA in FLCN ‐related RCC s was 23‐fold more abundant than in sporadic tumors. The distinctive expression patterns of GPNMB and FLCN might identify patients with RCC s who need further work‐up for BHD .