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

From the Departments of Urology, Microbiology and Immunology, and Pathology, College of Medicine, and Department of Statistics, National Cheng Kung University, Tainan, Taiwan, Republic of China, and Department of Otolaryngology, Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.

Address reprint requests to Nan-Haw Chow, MD, Department of Pathology, National Cheng Kung University Hospital, 138 Sheng-Li Rd, Tainan 704, Taiwan, Republic of China; email: chownh@ mail.ncku.edu.tw.

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.

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