Histologic Effects of Short Term Progestin Therapy on Endometrioid Adenocarcinoma
RJ Zaino, WE Brady, W Todd, K Leslie, E Fischer, H Ball. Hershey Med Ctr, Hershey; GOG, Buffalo; U Iowa Med Ctr, Iowa City; UNM, Albuquerque; U Mass Med Ctr, Worcester
Background: Some recurrent endometrial carcinomas respond to hormonal therapy, but prediction of response is imperfect, its duration is usually short, and the mechanism is unknown. We wished to determine the efficacy of progestins to induce a histologic response in endometrioid carcinomas and explore its effects on immunohistochemical measures of growth and apoptosis.
Design: The Gynecologic Oncology Group initiated a study of 75 women with endometrioid endometrial adenocarcinoma, 60 of whom received medroxyprogesterone acetate for 21-24 days immediately prior to hysterectomy and have available slides. Initial biopsies and hysterectomies were H&E stained and immunostained for estrogen receptor (ER) and progesterone receptor (PR) (38 cases), Bcl-2, Mib-1, and cleaved caspase-3 (Casp3) (56 cases). Histologic response, including regression of characteristics of neoplasia, and presence of metaplasia, secretion, and decidual change was assessed, and semi-quantitative scores (0-3+) of immunohistologic variables of initial biopsies were compared to post treatment slides.
Results: Only 1 complete histologic response was seen, but 37 tumors had a partial response (more often in tumors of initial lower grade, p<0.05), reflected by increased eosinophilic cytoplasm and luminal secretion. Decidual change was sometimes prominent but limited to the stroma surrounding benign glands. About 90% of tumors were initially ER and PR positive. ER and PR were significantly down-regulated as was Mib-1. Although Bcl-2 decreased following therapy, Casp3 did not change significantly.
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