Membranous staining of β-catenin and E-cadherin expression in patients with gastric cancer

Background: beta-catenin and E-cadherin are adhesion molecules that promote metastatic potential through epithelial-mesenchymal transition (EMT). Although they have not been extensively studied in gastric cancers, they represent potential testable prognostic markers. Methods: We explored the association between the immunohistochemical expression of these markers and clinicopathologic parameters by retrospectively reviewing 205 cases of gastric cancer from tissue microarrays (TMA). A method was developed to evaluate for membranous staining of beta-catenin and E-cadherin using grading criteria that characterized both the intensity of staining and the percentage of cells with loss of staining. Results: Weak membranous expression of E-cadherin and beta-catenin were associated with worse overall survival (p<0.05). Abnormal expression of E-cadherin and beta-catenin were significantly associated with each other (p<0.01). Loss of and/or weak membranous staining for both E-cadherin and beta-catenin was significantly associated with advanced cancer stage T2-T4 (versus stage T1, p<0.05) and tumors that are negative for H pylori infection (p<0.05). In addition, loss of and/or weak membranous staining for beta-catenin was significantly associated with poorly differentiated tumors (p<0.05), diffuse Lauren-type gastric tissue (p=0.02), and tumors with a significantly higher rate of lymphovascular invasion (p=0.02). Conclusion: Loss of/weak membranous expression of both E-cadherin and beta-catenin was associated with poorer overall survival rates and clinicopathologic parameters that indicated an aggressive clinical behavior. beta-catenin shows significant associations with more clinical parameters, making it a better biomarker than E-cadherin. In our multivariate analysis, weak intensity of staining of beta-catenin was an independent prognostic factor for survival and may be a useful immunohistochemical prognostic marker for patients with gastric cancer.