Claudin-10 Expression Is Increased in Endometriosis and Adenomyosis and Mislocalized in Ectopic Endometriosis

Abstract

Claudins, as the major components of tight junctions, are crucial for epithelial cell-to-cell contacts. Recently, we showed that in endometriosis, the endometrial epithelial phenotype is highly conserved, with only minor alterations. For example, claudin-11 is strongly expressed; however, its localization in the endometriotic epithelial cells was impaired. In order to better understand the role of claudins in endometrial cell-to-cell contacts, we analyzed the tissue expression and localization of claudin-10 by immunohistochemistry analysis and two scoring systems. We used human tissue samples (n = 151) from the endometrium, endometriosis, and adenomyosis. We found a high abundance of claudin-10 in nearly all the endometrial (98%), endometriotic (98–99%), and adenomyotic (90–97%) glands, but no cycle-specific differences and no differences in the claudin-10 positive endometrial glands between cases with and without endometriosis. A significantly higher expression of claudin-10 was evident in the ectopic endometrium of deep-infiltrating (p < 0.01) and ovarian endometriosis (p < 0.001) and in adenomyosis in the cases with endometriosis (p ≤ 0.05). Interestingly, we observed a shift in claudin-10 from a predominant apical localization in the eutopic endometrium to a more pronounced basal/cytoplasmic localization in the ectopic endometria of all three endometriotic entities but not in adenomyosis. Significantly, despite the impaired endometriotic localization of claudin-10, the epithelial phenotype was retained. The significant differences in claudin-10 localization between the three endometriotic entities and adenomyosis, in conjunction with endometriosis, suggest that most of the aberrations occur after implantation and not before. The high similarity between the claudin-10 patterns in the eutopic endometrial and adenomyotic glands supports our recent conclusions that the endometrium is the main source of endometriosis and adenomyosis.

Expression Differences Between the Eutopic Endometrium With and Without Endometriosis and the Ectopic Endome-trium. A Re-Analysis of Arrays

“…Similarly, we found a high abundance (~98%) of claudin-10 in nearly all endometrial and endometriotic glands, but no differences in the claudin-10 positive endometrial glands between cases with and without endometriosis [57]. A significantly higher expression of claudin-10 was detected in the ectopic endometrium of deep infiltrating and ovarian endometriosis [57]. Interestingly, a shift in claudin-10 from a predominant apical localization in the eutopic endometrium to a more pronounced basal/cytoplasmic localization in the ectopic endometria of all three endometriotic entities (ovarian, peritoneal, deep infiltrating) was observed.…”

“…In contrast to two reports that described an impaired expression of claudin-3 in endometriosis [54,55], we recently found an unchanged protein localization in the eutopic endometrium with and without endometriosis and also in the ectopic endometrium [56] which might be due to different fixation protocols used. Similarly, we found a high abundance (~98%) of claudin-10 in nearly all endometrial and endometriotic glands, but no differences in the claudin-10 positive endometrial glands between cases with and without endometriosis [57]. A significantly higher expression of claudin-10 was detected in the ectopic endometrium of deep infiltrating and ovarian endometriosis [57].…”

“…Interestingly, a shift in claudin-10 from a predominant apical localization in the eutopic endometrium to a more pronounced basal/cytoplasmic localization in the ectopic endometria of all three endometriotic entities (ovarian, peritoneal, deep infiltrating) was observed. Of note, despite the impaired endometriotic localization of claudin-10, the epithelial phenotype was retained in all glands [57].…”

Neutrophil gelatinase-associated lipocalin serum level: A potential noninvasive biomarker of endometriosis?

“…[21] In our study, we evaluated the immunostaining score for NGAL expression for the first time in the literature and found that NGAL expression was significantly higher in endometriosis cases than in the control group. As an example of the immunohistochemical scoring study similar to our study, Löffelman AC et al [22] investigated the expression of Claudin 10 in a study Early diagnosis and treatment of endometriosis both prevent the development of malignancy and endometriosis-related complications such as infertility and pain. Therefore, it is important to establish the diagnosis with new, rapid and noninvasive biomarkers.…”

“…In our study, we evaluated the immunostaining score for NGAL expression for the first time in the literature and found that NGAL expression was significantly higher in endometriosis cases than in the control group. As an example of the immunohistochemical scoring study similar to our study, Löffelman AC et al [ 22 ] investigated the expression of Claudin 10 in a study on human endometrium, endometriosis and adenomyosis tissue samples. Claudins are the major component of tight junctions and play a role in the escape of cancer cells out of the tissue.…”