Overexpression of c-met as a Prognostic Indicator for Transitional Cell Carcinoma of the Urinary Bladder: A Comparison With p53 Nuclear Accumulation

Abstract

PURPOSE: The c-met proto-oncogene encodes a receptor tyrosine kinase (Met) and has been shown to play a role in oncogenesis. Given that high titers of hepatocyte growth factor, the specific ligand for Met, are excreted in the urine and tend to reflect disease activity of bladder cancer, we performed this study to examine the clinical significance of Met in human bladder cancer. MATERIALS AND METHODS: We studied the mRNA expression and genomic alteration of c-met in five bladder cancer cell lines. Significance of Met overexpression was then compared with p53 nuclear accumulation (TP53) in primary bladder cancer (n = 142 patients). RESULTS: Expression of c-met mRNA tended to positively correlate with differentiation of cancer cell lines in the absence of point mutation. High expression of Met was found in seven cases (4.9%), low expression in 32 cases (22.5%), and negative expression in 103 cases (72.5%). Expression of Met was positively associated with histologic grade, stage classification, tumor size, and nodular tumor growth (P < .05, respectively); however, it was not related to TP53 status. Factors that predicted disease progression were tumor stage, Met status, and TP53 accumulation (P < .05, respectively). Indicators for poor long-term survival were invasive cancer, multiple tumors, and Met overexpression (P = .0006, .01, and .04, respectively). CONCLUSION: The c-met proto-oncogene plays a more important role in the progression of bladder carcinogenesis than p53. Evaluation of Met expression could identify a subset of bladder cancer patients who may require a more intensive treatment strategy.