Altered gamma-catenin expression correlates with poor survival in patients with bladder cancer.

We studied the expression of alpha-, beta-, gamma- catenin and E-cadherin in transitional cell carcinoma (TCC) and normal bladder epithelium and correlated these results with pathological and clinical parameters. We used an avidin-biotin immunoperoxidase technique to examine the cellular localization of alpha-catenin, beta-catenin, gamma-catenin and E-cadherin in 68 TCC and 14 normal bladder biopsies. E-cadherin, alpha-catenin, beta-catenin and gamma-catenin were expressed in a normal membranous pattern in all normal bladder epithelium specimens. Loss of normal surface E-cadherin, alpha-catenin, beta-catenin and gamma-catenin expression was found in 52/68 (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 between the loss of normal membranous expression of catenins and E-cadherin 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). E-cadherin-gamma-catenin complex may be a useful prognostic marker in bladder cancer. Work is in progress to establish whether normal membranous catenin expression can be enhanced by gene transfer or biological therapy to induce a less invasive and metastatic phenotype.