C-met proto-oncogene 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 hypothesized 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 protein in benign and malignant human renal tissues, and 2) correlate the presence of c-met protein with renal carcinoma histological subtype, tumor stage and tumor grade. Materials and Methods: Immunohistochemical analysis of c-met protein was performed in 41 normal and malignant human renal samples. Results: c-met Immunostaining was detected in the normal kidney tissue in all 41 samples. In the normal kidney c-met immunostaining was limited to the cell membrane and/or cytoplasm of epithelial cells in specific tubular segments, including the proximal convoluted tubule, thin and thick limbs of the loop of Henle, and the collecting duct. The glomeruli, distal convoluted tubule and stroma were consistently negative for c-met staining. c-met Immunostaining was detected in 68% of renal cell carcinomas and was more common in higher nuclear grade cancers (p <0.034). Conclusions: The c-met receptor is present in specific tubular segments in the normal kidney and is frequently expressed in higher nuclear grade renal cancers, suggesting a role in renal carcinoma progression. Future studies should evaluate the biological significance of the HGF/SF-c-met pathway in normal renal physiology, and renal cancer growth and progression.