Immunohistochemical analysis of the peritoneum adjacent to endometriotic lesions using antibodies for Ber-EP4 antigen, estrogen receptors, and progesterone receptors: implication of peritoneal metaplasia in the pathogenesis of endometriosis.

This study was designed to investigate whether or not the pelvic peritoneum exhibits a metaplastic process into müllerian-type epithelium using a marker for epithelial differentiation (Ber-EP4 antigen) and markers that indicate müllerian differentiation (estrogen receptors and progesterone receptors). The peritoneum and/or ovarian surface epithelium adjacent to endometriotic lesions were obtained from 24 patients with endometriosis at operation, and peritoneum and ovarian surface epithelium without any lesions were also obtained from control patients without endometriosis. The specimens were immunohistochemically analyzed using antibodies for epithelial antigen Ber-EP4, estrogen receptor (ER), and progesterone receptor (PR) on frozen sections. Normal peritoneal mesothelium showed negative staining for Ber-EP4, ER, and PR. The mesothelium of the peritoneum adjacent to the endometriotic lesions showed focal positivity for Ber-EP4, ER, and PR. Several cases of ovarian surface epithelium from normal control ovaries and ovaries adjacent to endometriotic lesions also showed focal positivity for Ber-EP4, ER, and PR. Stromal cells accompanying these foci were sporadically positive for ER and/or PR but negative for Ber-EP4. Focal expression of Ber-EP4, ER, and PR in the mesothelium of the peritoneum and the ovarian surface epithelium adjacent to endometriotic lesions suggests that mesothelium possibly acquires characteristics of epithelial as well as müllerian-type nature. These results support an existence of a metaplastic process of the peritoneal mesothelium in the pathogenesis of endometriosis. The more frequent Ber-EP4 positivity in normal ovarian surface epithelium compared to normal peritoneal mesothelium also suggests a fundamental difference in these tissues that may be related to the greater prevalence of epithelial neoplasms arising in ovarian tissue.