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 endometrium from women with polycystic ovarian syndrome (PCOS) and endometrial hyperplasia and adenocarcinoma.


METHODS
This is a retrospective study of 59 samples 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)-alpha, a marker of cell proliferation (Ki67), and another marker of early estrogen action, cFos. Regulation of Cyr61 protein was studied in a steroid-responsive endometrial 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, endometrial cancer patients, and hyperplasia patients.


CONCLUSIONS
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 adenocarcinoma in this group of women.
MacLaughlan
Shannon D
SD
Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Palomino
Wilder A
WA
Mo
Bilan
B
Lewis
Terrence D
TD
Lininger
Ruth A
RA
Lessey
Bruce A
BA
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015415:Biomarkers; D055515:Cysteine-Rich Protein 61; D004714:Endometrial Hyperplasia / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies
D015415:Biomarkers; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D004967:Estrogens; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger