Expression of e-cadherin and catenins in early gastric cancer

E-cadherin and its associated cytoplasmic proteins including alpha-, beta-, and gamma-catenin play a pivotal role in the maintenance of normal tissue architecture and the suppression of cancer invasion. The purpose of this study was to evaluate the expression of E-cadherin and alpha-, beta-, and gamma-catenin in a larger sample of early gastric cancer, and to examine the relation between these expressions and various clinicopathologic variables. The expression of E-cadherin and alpha-, beta-, and gamma-catenin was investigated using immunohistochemical technique with formalin-fixed, paraffin-embedded tissue specimens obtained from 108 patients who underwent surgery for early gastric cancer. In the gastric mucosa of noncancerous areas, epithelial cells showed equally strong membranous expression of E-cadherin and alpha-, beta-, and gamma-catenin proteins at the cell-cell boundaries. Reduced expression of E-cadherin and alpha-, beta-, and gamma-catenin was demonstrated in 43.5%, 39.8%, 42.6%, and 50% of cancer tissues, respectively. Whereas 34 tumors (31.5%) displayed preserved expression of all four E-cadherin-catenin complex components, 21 tumors (19.4%) displayed reduced expression of all components of this complex. Reduced expression of E-cadherin and alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal types of cancer, and decreased expression of E-cadherin and alpha-, beta-, and gamma-catenin correlated with poor differentiation. The expression of E-cadherin and beta- and gamma-catenin did not correlate with the patient's age, gender, tumor size, location, macroscopic type, depth of invasion, or lymph node metastasis. Only reduced expression of alpha-catenin correlated with lymph node metastasis. Reduced expression of all four E-cadherin-catenin complex components correlated with poorly differentiated and diffuse-type cancers, but not with the patient's age, gender, tumor size, location, macroscopic type, depth of invasion, or lymph node metastasis. These results suggest that dysfunction of the E-cadherin-catenin complex occurs in an early stage of carcinogenesis, playing a crucial role in disruption of tissue architecture and loss of differentiation in early gastric cancer.