Endometrial expression of Cyr61:: A marker of estrogenic activity in normal and abnormal endometrium

OBJECTIVE: To compare the expression of Cyr61 in normal cycling endometrium with enclometrium from women with polycystic ovarian syndrome (PCOS) and enclometrial hyperplasia and adenocarcinoma. METHODS: This is a retrospective study of 59samples of normal and abnormal endometrium. Endometrial biopsies were obtained from normal fertile controls throughout the menstrual cycle and compared with endometrium from ovulatory and anovulatory women with PCOS and complex endometrial hyperplasia and endometrioid adenocarcinoma. Cyr61 expression was evaluated by using immunohistochemistry and reverse transcription PCR for Cyr61, estrogen receptor (ER)-cL, a marker of cell proliferation (Ki67), and another marker of early estrogen action, cFos. Regulation of Cyr61 protein was studied in a steroidresponsive enclometrial carcinoma cell line, ECC1. RESULTS: Cyr61 protein was regulated by estrogen. In normal endometrium, Cyr61 was highest in the proliferative phase and lowest in the normal midsecretory phase. In contrast, elevated levels of Cyr61, ER-alpha, Ki67, and cFos were all found in the midsecretory endometrium of ovulatory PCOS patients, enclometrial cancer patients, and hyperplasia patients. CONCLUSION: Cyr61 is overexpressed in PCOS endometrium, reflecting a heightened responsiveness to estrogen. As a unique marker of estrogen action, Cyr61 may be an early biomarker for the development of hyperplasia or adenocarcinorna in this group of women.