Expression of Membrane-Type 2 and 3 Matrix Metalloproteinases in Endometriosis and Adenomyosis

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases capable of degrading the different components of the extracellular matrix, and are involved in different physiological processes such as cell proliferation, differentiation, angiogenesis, apoptosis and cell migration. Dysregulation of MMPs has been reported in a number of cancers. Consequently, we postulate that this might be replicated in the pathogenesis of endometriosis, since the two conditions share similar developmental stages. We invested in the expression pattern of MT2-MMP and MT3-MMP in ectopic endometrium of persons with and without endometriosis as well as their possible role in the pathogenesis of endometriosis. Tissue samples were obtained after surgery from healthy endometrium, endometrium with endometriosis and adenomyosis, deep infiltrating endometriosis (DIE), peritoneal endometriosis (PE) and ovarian endometriosis (Ov). Expression of the MT-MMPs was determined using immunohistochemistry. Both proteins were expressed in the glandular and luminal epithelial cells of endometrium of persons with and without endometriosis. There was no cycle-dependent differences in the endometrium of persons with and without endometriosis. Interestingly, there was enhanced expression of both MT2-MMP and MT3-MMP in adenomyosis. In contrast, MT2-MMP there was decreased in ovarian, peritoneal and DIE, decreased MT3-MMP in peritoneal and DIE compared to eutopic endometrium and adenomyosis. The equal expression of MT-MMPs in endometrium of persons with and those without endometriosis in contrast to the impaired expression in adenomyosis and ectopic lesions suggest that the changes occurred after and not before implantation. The altered expression of MT2-MMP and MT3-MMP in adenomyosis and ectopic endometrium suggest distinct interactions in the different environments.