Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.
Bottom Line: Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder associated with a germline mutation of the folliculin gene (FLCN).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.
Affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.Show MeSH
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Mentions: Immunostaining revealed that GPNMB was undetectable in normal control kidneys (Fig.6). All FLCN-related RCCs (except for three non-chromophobe RCCs) were positively stained for GPNMB (Table2, Fig.6b,d). Immunostaining intensities of GPNMB were correlated with the relative expression of GPNMB mRNA, such that BHD15 with intense staining showed the highest expression whereas BHD2 with moderate staining showed lower expression compared with BHD15. Small nodules of renal oncocytosis in non-tumor regions, which is one of the diagnostic characteristics of BHD kidneys,5 also showed moderate immunostaining (Fig.6f). In sporadic cases, half of the chromophobe RCCs and most other types were negatively stained for GPNMB (Table3). Importantly, all sporadic oncocytomas were negative for GPNMB, whereas all HOCTs in BHD were positively stained. With regard to GPNMB-positive RCCs, all but one showed nuclear staining for FLCN. Only one GPNMB-positive RCC showed cytoplasmic staining for FLCN. The patient with this tumor also had a few pulmonary cysts. Genetic testing was carried out and the possibility of BHD was eliminated.
Affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.