ALTERED GAMMA-CATENIN EXPRESSION CORRELATES WITH POOR SURVIVAL IN PATIENTS WITH BLADDER-CANCER

Purpose: We studied the expression of alpha-, beta-, gamma- catenin an d E-cadherin in transitional cell carcinoma (TCC) and normal bladder e pithelium and correlated these results with pathological and clinical parameters. Materials and Methods: We used an avidin-biotin immunopero xidase technique to examine the cellular localization of alpha-catenin , beta-catenin, gamma-catenin and E-cadherin in 68 TCC and 14 normal b ladder biopsies. Results: E-cadherin, alpha-catenin, beta-catenin and gamma-catenin were expressed in a normal membranous pattern in all nor mal bladder epithelium specimens. Loss of normal surface E-cadherin, a lpha-catenin, beta-catenin and gamma-catenin expression was found in 5 2/68 (76.4%) tumors, 57/68 (83.8%) tumors, 54/68 (79.4%) tumors and 54 /68 (79.4%) tumors (p <0.001). There was a significant correlation bet ween the loss of normal membranous expression of catenins and E-cadher in and increased grade (p <0.05). A highly significant correlation was observed between the loss of expression of E-cadherin, alpha- catenin and gamma-catenin, but not beta-catenin, with increased TNM stage (p <0.05). The abnormal expression of gamma-catenin as well as E-cadherin was correlated with poor survival (p <0.05). Conclusions: E-cadherin- gamma-catenin complex may be a useful prognostic marker in bladder can cer. Work is in progress to establish whether normal membranous cateni n expression can be enhanced by gene transfer or biological therapy to induce a less invasive and metastatic phenotype.