C-MET PROTOONCOGENE EXPRESSION IN BENIGN AND MALIGNANT HUMAN RENAL TISSUES

Purpose: Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen to renal epithelial cells in vitro and in vivo. HGF/SF signals through its receptor which is coded by the c-met proto-oncogene. We h ypothesized that altered expression of the HGF/SF receptor, c-met, may be involved in the pathogenesis of certain renal cell carcinomas. Our objectives were to 1) assess the presence and localization of c-met p rotein in benign and malignant human renal tissues, and 2) correlate t he presence of c-met protein with renal carcinoma histological subtype , tumor stage and tumor grade. Materials and Methods: Immunohistochemi cal analysis of c-met protein was performed in 41 normal and malignant human renal samples. Results: c-met Immunostaining was detected in th e normal kidney tissue in all 41 samples. In the normal kidney c-met i mmunostaining was limited to the cell membrane and/or cytoplasm of epi thelial cells in specific tubular segments, including the proximal con voluted tubule, thin and thick limbs of the loop of Henle, and the col lecting duct. The glomeruli, distal convoluted tubule and stroma were consistently negative for c-met staining, c-met Immunostaining was det ected in 68% of renal cell carcinomas and was more common in higher nu clear grade cancers (p < 0.034), Conclusions: The c-met receptor is pr esent in specific tubular segments in the normal kidney and is frequen tly expressed in higher nuclear grade renal cancers, suggesting a role in renal carcinoma progression, Future studies should evaluate the bi ological significance of the HGF/SF-c-met pathway in normal renal phys iology, and renal cancer growth and progression.