Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth

Various genetic changes are involved in human renal cell carcinomas (RCCs). However, the molecular events related to other cytomorphological subtypes of RCC are not well known, apart from the relationship between the von Hipp el-Lindau tumour suppressor gene and clear cell subtype RCC. We examined th e overexpression of several growth factor receptors immunohistochemically a nd analyzed their relationship to the cytomorphological characters in 120 c ases of RCCs. These receptors included c-met proto-oncogene product (c-MET) , epidermal growth factor receptor (EGFR) and transforming growth factor be ta receptor II (TGT beta R). The overexpression of c-MET was detected in al l cases (20/20) of the tubulo-papillary growth type and 78.3% (18/23) of ch romophilic cell subtype, resulting in a very significant associations betwe en c-MET overexpression and tubulo-papillary growth RCCs (P<0.0001), c-MET and chromophilic subtype RCCs (P<0.0001), and c-MET and EGFR (P<0.0001). EC FR overexpression was significantly associated with the compact growth RCCs (49/89, P<0.0001), clear cell subtype RCCs (P<0.005) and the overexpressio n of TGF beta R (P<0.0001). These results strongly suggest a close correlat ion between the overexpression of c-MET and development of the chromophilic subtype of RCC with papillary growth pattern. EGFR expression is closely r elated to the pathogenesis of the clear cell subtype of RCC with compact gr owth pattern. The overexpression of c-MET, EGFR, and TGF beta R may have ro les that are individually significant in the morphogenesis of RCC.