Diseases of the Reproductive System
(W207) EXPRESSION OF AN EXTRACELLULAR MATRIX METALLOPROTEINASE-INDUCER (BASIGIN) IN OVARIAN ENDOMETRIOSIS.
McDonnel Smedts, Anna1, Lele, Subodh1, Modesitt, Susan1, Curry, Thomas1, 1 University of Kentucky, Lexington, KY
ABSTRACT- Ovarian endometriosis, the ectopic implantation of endometrial tissue onto the ovary, is a significant causative factor of infertility and morbidity. Although the matrix metalloproteinases (MMP) have been implicated in the etiology of this disease, the mechanisms regulating this system remain poorly understood. Basigin (Bsg, also known as EMMPRIN/CD147) is involved in the induction of MMP (proteolytic) activity in normal endometrium; therefore, our objectives were to characterize its expression in ovarian endometriotic tissue, normal ovary, and eutopic endometrium during the menstrual cycle. Subsequent studies addressed the localization of MMP2 and MMP9 in adjacent sections. Biopsies of benign ovarian endometriotic lesions, normal ovarian tissue, and endometrium were obtained from the same patient during either the proliferative (n = 5) or secretory (n = 5) phases of the menstrual cycle and processed for immunohistochemical analysis. BSG was detected in glandular epithelia and stroma of endometriotic lesions from both menstrual phases; no distinct patterns of expression were evident between groups. In proliferative-phase endometriotic tissue, BSG typically localized to the basal aspect and intercellular regions of the glandular epithelial layer. Cytoplasm and plasma membranes of stromal cells labeled intensely at endometriotic foci. In endometriotic tissue collected during the secretory phase, glandular epithelia labeled sporadically while stromal tissue stained relatively consistently. Adjacent ovarian stroma lacked Bsg expression; however, BSG labeling was apparent in corpora lutea and in follicular theca and granulosa cells. In all samples, the luminal epithelium of eutopic endometrium exhibited specific, intense immunolabeling. Mmp9 and Mmp2 expression was detected in the cytoplasm and cell membranes of the glandular epithelia as well as in stromal cells of endometriotic tissue; increased immunoreactivity of MMP2 in the glandular epithelia was noted in tissues collected during the proliferative phase. The current data demonstrate unique expression patterns of Bsg in the human ovary, endometrium, and in endometriotic tissue, and support a possible role for BSG as a mediator in the dysregulation of proteolytic MMPs in endometriosis. NIH P20RR15592
KEY WORDS: endometriosis, basigin, metalloproteinase