Intratumoral effects of medroxy-progesterone on proliferation, apoptosis, and sex steroid receptors in endometrioid endometrial adenocarcinoma

OBJECTIVE: The effects of progesterone on proliferation and apoptosis are studied in a scrutinized evaluation of endometrial carcinoma before, during, and after progesterone therapy. The heterogeneity of sex steroid expression as well as proliferation, indicated as Ki-67 index, is considered. METHODS: A total of 29 endometrial carcinomas were studied with in situ evaluation of Ki-67 proliferation marker, estrogen and progesterone receptors (ER and PR), and bcl-2 and p53 immunohistochemistry in the epithelial part of the tumor. In biopsy 1, before the therapy, Ki-67 ER, and PR were studied also in stroma. Apoptotic cells were morphologically identified in hematoxylin- and eosin-stained sections of the tumors and the apoptotic index (apoptotic cells per 1000 cells) was calculated. Chances in feature factors were mainly evaluated by repeated measures ANOVA. RESULTS: Proliferation (Ki-67) was decreased in grade 1 (G1) and grade 2 (G2) tumors during progesterone therapy both in overall evaluation (Ki) and particularly in the areas of maximal proliferation (Ki-max). No change was seen in G3 tumors. A decrease in PR expression in the areas of maximal expression for PR (PR-max) was also observed in G1 and G2 tumors. Apoptosis as well as bcl-2 and ER expression were unchanged during therapy and withdrawal. CONCLUSIONS: The effect of progesterone is seen only on proliferation in low-grade (G1 and G2) tumors. The coexistence of high PR expression in the foci of high proliferation may contribute to the effect in G1 and G2 tumors. No effect of progesterone is seen on apoptosis in tumors of any grade.