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

Background: β-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 β-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 β-catenin were associated with worse overall survival (<0.05). Abnormal expression of E-cadherin and β-catenin were significantly associated with each other (<0.01). Loss of and/or weak membranous staining for both E-cadherin and β-catenin was significantly associated with advanced cancer stage T2-T4 (versus stage T1, <0.05) and tumors that are negative for infection (<0.05). In addition, loss of and/or weak membranous staining for β-catenin was significantly associated with poorly differentiated tumors (<0.05), diffuse Lauren-type gastric tissue (=0.02), and tumors with a significantly higher rate of lymphovascular invasion (=0.02).

Conclusion: Loss of/weak membranous expression of both E-cadherin and β-catenin was associated with poorer overall survival rates and clinicopathologic parameters that indicated an aggressive clinical behavior. β-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 β-catenin was an independent prognostic factor for survival and may be a useful immunohistochemical prognostic marker for patients with gastric cancer.