Histological and Immunohistochemical Characterization of the Similarity and Difference Between Ovarian Endometriomas and Deep Infiltrating Endometriosis

Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) have long been recognized to have different histology and, as such, postulated to be 2 separate disease entities. Few studies, however, have attempted to elucidate the causes for their differences. Making use of ectopic endometrial tissue samples from 25 and 20 women with OMA and DIE, respectively, and control endometrial tissue samples from 25 women without endometriosis, we conducted an immunohistochemical analysis to evaluate the expression of a group of carefully chosen markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), fibrosis, vascularity, hormonal receptors, and proteins involved in epigenetic modifications. We found that both OMA and DIE lesions exhibited the same cellular changes consistent with EMT, FMT, SMM, and fibrosis as already shown in animal models. Compared to OMA, DIE lesions underwent more thorough and extensive EMT, FMT, and SMM and, consequently, displayed significantly higher fibrotic content but less vascularity. The 2 conditions also showed different expression levels of hormonal receptors. Both OMA and DIE lesions, especially the latter, showed significantly higher staining of enhancer of zeste homolog 2, H3K9me3, and H3K27me3 than that of control endometrium, suggesting progressive epigenetic changes concomitant with cellular ones. Finally, proteins that are known to be involved in fibrogenesis, such as thymocyte differentiation antigen 1 and peroxisome proliferator-activated receptor , were also aberrantly expressed under both conditions. The many similarities shared by both OMA and DIE indicate that the 2 conditions may actually share the same pathogenesis/pathophysiology. Their differences, however, suggest that the source of these differences may result from the different lesional microenvironments.