E-cadherin is a Ca(2+)-dependent intercellular adhesion molecule known to exert an invasion-suppressor function. In the present study, E-cadherin expression was immunohistochemically investigated in a retrospective series of 413 RO-resected gastric carcinomas using the monoclonal antibody (MAb) 5H9. Of these cases, 108 tumors revealed a preserved E-cadherin expression similar to that of normal gastric mucosa. In 95 tumors, E-cadherin expression was moderately reduced and in 86 tumors highly reduced. In 124 tumors, no or only a very weak dotted expression could be detected. There was a significant correlation between the degree of E-cadherin expression and the grade of tumor differentiation, as well as with histological type according to the Laurén and the WHO classifications. In contrast, no correlation could be demonstrated between E-cadherin expression and the prognostic parameters depth of invasion, lymph node involvement and vascular invasion. As shown by univariate Cox regression analysis, patients with E-cadherin-positive tumors had significantly better 3-and 5-year survival rates than patients with E-cadherin-negative tumors. This prognostic impact remained present in a multivariate Cox regression analysis, including the prognostic parameters pT category, pN category and vascular invasion.