Frequent occurrence of abnormal E-cadherin/beta-catenin protein expression in advanced gallbladder cancers and its association with decreased apoptosis

Abstract

Objective: Our aim is to assess the clinicopathological significance of E-cadherin and beta-catenin expression, as well as their association with apoptosis in gallbladder cancers.

Methods: The expression of E-cadherin and beta-catenin proteins was examined in 4 biliary tract cancer cell lines and 49 gallbladder cancer specimens by immunofluorescent or immunohistochemical methods and Western blotting. The apoptotic status was evaluated in the cell lines by poly(ADP-ribose) polymerase Western blotting and in the tumors by the TdT-mediated dUTP nick end labeling assay.

Results: Expression of poly(ADP-ribose) polymerase (apoptosis) was only seen in cell lines that expressed both E-cadherin and beta-catenin. Reduced expression of E-cadherin and beta-catenin was frequently seen in advanced gallbladder cancer cases (61 and 83%, respectively) relative to pT1 cases (25 and 63%, respectively). The 5-year survival rate in cases with reduced E-cadherin expression was 26%, significantly lower than in cases with preserved E-cadherin expression (70%; p = 0.017). Cases with reduced expression of both had lower apoptotic indices and showed a worse prognosis compared with cases with reduced expression of either E-cadherin or beta-catenin (p = 0.04 and 0.049, respectively).

Conclusions: The expression of E-cadherin or beta-catenin frequently diminishes as the tumor progresses, and abnormalities of E-cadherin and beta-catenin expression were associated with decreased apoptosis in gallbladder cancers. E-cadherin expression might be a useful prognostic marker in this tumor.