Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer.

E-cadherin function is thought to be impaired in epithelial cancer. To investigate the alterations in E-cadherin associated with cytoplasmic molecules including alpha-catenin, beta-catenin, gamma-catenin, p120CAS, and IQGAP1 in various endometrial cancers with different degree of differentiation, we examined the localization and expression of E-cadherin and cytoplasmic molecules in 30 cases of both well and poorly differentiated endometrioid adenocarcinomas, using immunofluorescence and immunoblotting techniques. E-cadherin and cytoplasmic molecules demonstrated linear staining at the cell boundaries in normal endometrium. In all 20 cases with well differentiated adenocarcinomas, alpha-catenin and IQGAP1 disappeared from the cell adhesive sites, but other cytoplasmic molecules were co-localized with E-cadherin along the cell boundaries. In all 10 cases with poorly differentiated adenocarcinomas, E-cadherin and cytoplasmic molecules accumulated as large aggregates along cell adhesive sites, and the localization of IQGAP1 differed from those of other cytoplasmic molecules. The expression of these molecules in all 20 cases with well differentiated adenocarcinomas decreased or was lost in Triton-insoluble fraction, in comparison with the findings for all cases with normal endometrium or poorly differentiated adenocarcinomas. These results suggested that each alteration in E-cadherin associated with cytoplasmic molecules may play a different role in E-cadherin dysfunction between well and poorly differentiated adenocarcinomas. Copyright 2000 Cancer Research Campaign.