Impaired expression of intercellular contact and adhesion proteins in endometrial hyperplasia, endometrial intraepithelial neoplasia, and low-grade endometrioid adenocarcinoma

Objective. To study the impaired expression of β-catenin, E-cadherin, and ezrin in different forms of endometrial hyperplasia, endometrial intraepithelial neoplasia, and low-grade endometrioid adenocarcinoma. Subjects and methods. Examinations were made in 45 patients who formed 5 groups: 1) simple endometrial hyperplasia (HE) (n = 12); 2) complex endometrial hyperplasia without atypia (CEH) (n = 9); 3) complex endometrial hyperplasia with atypia (CEHA) (n = 5); 4) endometrial intraepithelial neoplasia (EIN) (n = 5); 5) low-grade endometrioid adenocarcinoma (EAU) (n = 4). A control group consisted of 10 patients with the proliferative endometrium. The expression of Ki-67, PTEN, β-catenin, E-cadherin, and ezrin was immunohistochemically assessed. Results. As the disease progresses from simple HE to EAC, the loss of specific membrane localization of β-catenin, E-cadherin, and ezrin occurs, which reflects their lower functional activity. The altered localization of β-catenin, E-cadherin, and ezrin gives rise to impaired intercellular contacts during tumor progression. EIN has been established to be characterized by not only morphological features concurrent with the loss of PTEN expression, but also by the loss of membrane β-catenin, E-cadherin, and ezrin expression. Conclusion. The molecular and morphological features of CEHA and EIN are largely stereotypical, including the loss of membrane localization of β-catenin, E-cadherin, and ezrin from simple HE to EAC, but distinct in the expression of the β-catenin, E-cadherin, and ezrin genes in the cytoplasm of epithelial cells in EAC and in the expression of PTEN. Lower membrane β-catenin, E-cadherin, and ezrin expression in EAC may be related to the process of epithelial-mesenchymal transformation underlying a readiness for invasive growth in EIN and the invasive growth itself in EAC. The obtained results of clinicoanamnestic, diagnostic, and immunohistochemical studies in the above patient groups can substantiate a differential approach to choosing a treatment policy for patients with different forms of EH, EIN, and EAC.

endometrial hyperplasia, endometrial intraepithelial neoplasia, low-grade endometrioid adenocarcinoma, immunohistochemistry, β-catenin, E-cadherin, ezrin