Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors.

EpCam is an epithelial adhesion molecule expressed in a broad range of carcinomas. Clinical trials with specific humanized anti-EpCam antibodies have shown promising results and have been inaugurated in renal cell carcinoma (RCC) therapy. To study the EpCam expression profile, primary renal cell neoplasms as well as corresponding metastases were evaluated by immunohistochemistry in tissue microarrays. EpCam expression in oncocytomas and chromophobe RCCs was determined on conventional large sections. Moderate or strong EpCam expression was found in eighteen percent of clear cell (n=147), 75% of chromophobe (n=12), and 55% of papillary RCCs (n=20), but not in oncocytomas (n=3). On large sections, 90% of chromophobe RCCs (n=20) showed a strong and homogeneous positivity, whereas oncocytomas (n=15) revealed EpCam positivity in single tumor cells or small clusters. Fourteen percent of RCC metastases (n=97) showed EpCam expression. Patients with EpCam expressing clear cell RCC showed a trend toward a better prognosis in a Cox regression analysis including stage, grade, and necrosis. The data suggest EpCam as a potential therapeutic target in a subset of patients with RCC. In addition, expression patterns of EpCam could become a helpful tool in the discrimination of chromophobe RCC and oncocytoma.

Relevance of nuclear and cytoplasmic von hippel lindau protein expression for renal carcinoma progression.

Alterations of the von Hippel-Lindau tumor-suppressor gene (VHL) on 3p25-p26 are frequent in clear-cell renal-cell carcinoma (RCC). The VHL protein (pVHL) is implicated in cell-cycle control and gene regulation, and requires transcription-dependent nuclear-cytoplasmic trafficking for its function. There are two biologically active VHL protein isoforms: pVHL(30) and pVHL(19). To study prevalence, subcellular expression and biological significance of pVHL in renal tumors, tissue microarrays with renal-cell carcinomas were immunohistochemically examined for pVHL expression. Antibodies against both protein isoforms (anti-pVHL(30)/pVHL(19)) and against pVHL(30) (anti-pVHL(30); Ig33) were used. The anti-pVHL(30)/pVHL(19) antibody showed nuclear and cytoplasmic pVHL expression, whereas the anti-pVHL(30) antibody (Ig33) detected cytoplasmic pVHL expression, suggesting that the distribution of VHL protein isoforms varies in the nuclear and cytoplasmic compartments of renal tumors. There were 175 of 398 primary clear-cell RCCs (44%) with both nuclear and cytoplasmic pVHL expression. Seventy-seven clear-cell RCCs (19%) showed only nuclear, 22 (6%) showed only cytoplasmic, and 124 tumors (31%) showed no pVHL expression. Notably, combined nuclear and cytoplasmic pVHL expression was associated with low histological grade (P < 0.0001), early tumor stage (P < 0.01), and better prognosis (P < 0.01). These results imply that alteration of subcellular pVHL trafficking is of potential relevance for the biological behavior of clear-cell RCC.