Aberrant E-Cadherin and α-Catenin Expression in Prostate Cancer: Correlation with Patient Survival

Abstract

E-cadherin maintains the normal differentiated phenotype in epithelial cells; this function is partly mediated by α-catenin, which links E-cadherin to the cell cytoskeleton. Dysfunction of E-cadherin in vitro and in vivo is associated with an invasive phenotype. However, the role of α-catenin is largely undetermined. We analyzed the expression of E-cadherin and α-catenin in prostate cancer to assess the relationship of abnormal expression to stage, grade and survival. E-cadherin expression was evaluated in 99 prostate cancers. In 79 of those specimens, α-catenin was also assessed. In benign prostatic epithelium, both E-cadherin and α-catenin were expressed uniformly at the cell membrane. Abnormal E-cadherin expression was found in 56% of cancer specimens, whereas α-catenin expression was abnormal in 42%. Abnormal expression of each molecule was significantly correlated with Gleason score (P < 0.0001) and the ratio of resection chippings infiltrated by tumor (P < 0.0001). E-cadherin expression was also associated with the extent of disease on the initial bone scan (P = 0.017). Univariate analysis showed significantly lower survival rate for patients with abnormal E-cadherin (P = 0.0003) or α-catenin expression (P = 0.031). Multivariate regression analysis showed that the prognostic value of E-cadherin was independent of tumor grade but not of metastasis. These results suggest that perturbation of cell-cell adhesion is involved in the progression of prostate cancer and that analysis of E-cadherin expression may be clinically useful.