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.

Keywords: adenomyosis; claudin-10; endometriosis; endometrium.

Figure 1

Representative microphotographs of claudin-10 in the proliferative (A) and secretory (B) endometrium without endometriosis and in the proliferative (C) and secretory (D) endometrium with endometriosis. Two patients also had leiomyomas (A,C). One patient had endometriosis in the uterosacral ligament (C), and one patient had endometriosis in the bladder (D). gl, gland; str, endometrial stroma; le, luminal epithelium; lu, lumen; scale bars 100 µm; magnification 200×.

Figure 2

Representative microphotographs of claudin-10 in cases with matched endometrium and adenomyosis lesions. A proliferative endometrium (A) with the corresponding adenomyosis (C) and a secretory endometrium (B) with the corresponding adenomyosis (D) are presented. One patient also showed endometriosis in the vagina, rectum, and colon (A,C). The other patient presented with a leiomyoma (B,D). gl, gland; str, endometrial/adenomyotic stroma; myo, myometrium; arrows denote the boundaries of the adenomyotic lesions; scale bars 100 µm, magnification 200×.

Figure 3

Representative microphotographs of claudin-10 in ovarian endometriosis (A), ovarian cyst), peritoneal endometriosis ((B), pouch of Douglas), and DIE ((C), bladder). For a better comparison, a proliferative endometrium is also shown (D). PE, peritoneal endometriosis; DIE, deep-infiltrating endometriosis. lu, lumen; gl, gland; str, endometrial stroma; arrows denote the boundaries of the lesions; scale bars 100 µm, magnification 200×.

Figure 4

Representative microphotographs of claudin-10 showing the different localizations: apical ((A), a, score 5), apicolateral ((B), al, score 4), basolateral ((C), bl, score 3), mainly basal ((D), b, score 4), and cytoplasmic ((E), score 5). A representative negative control with the rabbit IgG isotype on the proliferative endometrium is provided (F). A secretory endometrium of a patient with leiomyoma (A), a secretory endometrium of a patient with endometriosis in the rectum (B), a secretory endometrium of a patient (C), a patient with peritoneal endometriosis in the utero-sacral ligament (D) and further lesions in the rectum and bladder, and a patient with DIE in the rectum (E) are shown. The arrows denote typical claudin-10 cellular localizations. Gl, gland; str, endometrial stroma; scale bars 50 µm (A–E) and 100 µm (F); magnification 400× (A–E) and 200× (F).