Endometriosis and adenomyosis In endometriosis the cell-to-cell contacts during epithelial-mesenchymal transition are intact

Abstract

Context Epithelial-mesenchymal transition (EMT) is an important process of cell remodelling during development and organogenesis, but also in diseases like cancer and fibrosis. It is defined by loss of the epithelial and gain of a mesenchymal phenotype, where cells often acquire migratory and invasive capabilities. Many reports also claimed EMT in the pathogenesis of endometriosis and described loss of cell-to-cell contacts, especially of claudin-3, -4 and -7. Objective In this study we analysed the cell-to-cell contacts, especially claudins, in patients without and with endometriosis in order to validate the suggested loss of the epithelial phenotype in endometriosis. Methods We performed an immunohistochemical study with antibodies against claudin-2, -3, -7 and -11 on tissue sections of patients with and without endometriosis and the three endometriotic entities, ovarian and pelvic endometriosis and deep infiltrating endometriosis (DIE). Quantification was done with the HSCORE. Main Outcome Only claudin-11 showed an impaired localization from the apicolateral junctions to a basal or basolateral localization in ovarian and peritoneal endometriosis, and DIE. Results We found a preferential localization of claudin-2/-3 in the glandular cells in the endometrium with and without endometriosis. Quantification of claudin-2/-3 showed no differences in eutopic endometrium of controls compared to cases with endometriosis and are also highly similarly in the ectopic compared to the eutopic endometrium. Furthermore, we identified claudin-7 primarily at the basolateral junctions of the glandular epithelial cells in eutopic and ectopic endometrium in nearly all glands and cysts. Quantification showed a slight increase of claudin-7 in peritoneal and DIE compared to eutopic endometrium. In contrast, claudin-11 was localized mainly in the apicolateral junctions in nearly all glandular epithelial cells of the eutopic endometrium. Interestingly, we observed a deregulation of claudin-11 localization to a basal or basolateral localization in ovarian (P<0.001), peritoneal (P<0.01), and DIE (P<0.05) and a moderately decreased abundance in ovarian endometriosis. Conclusions There was no loss of cell-to-cell contacts in the endometrial and endometriotic epithelial cells, only some changes in the localization of claudin-11 in ectopic endometrium. Thus, we suggest that only a partial EMT, without loss of the epithelial phenotype, is involved in the pathogenesis of endometriosis.