Prognostic Value of Cadherin-associated Molecules (α-, β-, and γ-Catenins and p120^cas) in Bladder Tumors

Abstract

Loss of E-cadherin-mediated adhesion is an important step in the progression of many carcinomas. In model systems, it has been shown that cadherin function requires not only proper E-cadherin expression but also its linkage to the cytoskeleton through catenins. Hence, defects in catenins may cause defective E-cadherin function, and catenins as well as E-cadherin might constitute prognostic indicators. Here, we extend our previous study on E-cadherin in bladder cancer (Cancer Res., 53: 3241–3245, 1993). We have evaluated the expression of E-cadherin-associated cytoplasmic molecules (α-, β-, and γ-catenins and p120^cas) to clarify whether or not the pattern of their expression could provide additional prognostic information beyond that from E-cadherin alone. Forty-eight frozen bladder tumor specimens and 9 samples of normal urothelium were studied by immunohistochemistry. A discrepancy between the E-cadherin and catenin expression pattern was seen in 20.8% of cases. Abnormal expression of each molecule is significantly correlated with tumor grade (P < 0.01) and stage (P < 0.01). Reduced expression of all of the molecules correlates with poor survival (P < 0.01 for each variable). Proportional hazard regression analysis showed that β-catenin, E-cadherin, and α-catenin have strong predictive value, whereas plakoglobin and p120^cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, α-catenin, or β-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, β-catenin, E-cadherin, and α-catenin have similar prognostic values. Therefore, from a practical point of view, the expression of any of these proteins can be of prognostic value for patients with bladder cancer.