Mesenchymal to epithelial transition in the human ovarian surface epithelium focusing on inclusion cysts

Abstract

Most ovarian cancers arise from the mesothelial surface lining of the ovaries or from invaginations of this lining into the superficial ovarian cortex that form cortical inclusion cysts. Thus, these cysts are thought to be precursor lesions of ovarian carcinoma. Epithelial-mesenchymal transition, which is a transcriptional program for inducing maintenance of the mesenchymal phenotype, acts in tumor progression and metastasis. Little is known about the mechanisms involved in mesenchymal-epithelial transition (MET). We aimed to characterize the human ovarian surface epithelium (OSE) and inclusion cysts by immunohistochemical analysis to examine whether MET occurs during inclusion cyst formation in the OSE. We used specimens from 9 endometrial cancer patients who had undergone hysterectomy and bilateral salpingo-oophorectomy. Immunohistochemical analysis was performed in 10 normal ovaries containing 92 inclusion cysts and in 4 normal tubes to examine the expression of antigen markers including calretinin, podoplanin, D2-40, thrombomodulin, HBME-1, vimentin, EMA, WT1, CA125, MOC31, TAG-72, Ber-EP4 and E-cadherin. The positive staining rates for mesothelial markers in normal OSE were 100% (10/10) for calretinin, 80% (8/10) for podoplanin, 80% (8/10) for D2-40, 70% (7/10) for thrombomodulin, 100% (10/10) for HBME-1, 100% (10/10) for vimentin. The positive staining rates for epithelial markers in tubal epithelium were 100% (4/4) for HBME-1, 100% (4/4) for vimentin, 100% (4/4) for EMA, 75% (3/4) for TAG-72, 100% (4/4) for Ber-EP4. Inclusion cysts showed positive staining for both markers with an incidence of 51% (47/92) for HBME-1, 44% (41/92) for vimentin, 65% (60/92) for TAG-72, 88% (81/92) for Ber-EP4. The OSE showed the characteristics of both mesenchymal and epithelium cells. In contrast, inclusion cysts gained epithelial characteristics, but lost mesenchymal characteristics. These findings support that MET occurs during the inclusion cyst formation from OSE.