The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1, estrogen-regulated genes implicated in proliferation, is increased in peritoneal endometriosis

Abstract

Objective: To analyze the expression of estrogen receptors α and β as well as their target genes implicated in proliferation, c-myc, cyclin D1, and GREB1, in the endometrium of women with or without endometriosis.

Design: Expression analysis in human tissue.

Setting: University hospitals and a clinic.

Patient(s): Ninety-one premenopausal women (59 patients with endometriosis and 32 controls) undergoing laparoscopic surgery.

Intervention(s): Biopsies were obtained at time of surgery, performed during the proliferative phase of the cycle.

Main outcome measure(s): Estrogen receptors α and β as well as c-myc, cyclin D1, and GREB1 mRNA expression levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Tissue localization of these estrogen-regulated genes was analyzed by immunohistochemistry.

Result(s): Estrogen receptors α and β as well as c-myc, cyclin D1, and GREB1 mRNA expression levels were increased in ectopic tissue in comparison with both normal and eutopic endometrium. Estrogen receptor mRNA levels also were upregulated in the eutopic peritoneal tissue of patients with endometriosis. Cyclin D1 and GREB1 expression was augmented in eutopic endometrium. c-myc, cyclin D1, and GREB1 proteins exhibited a nuclear localization in ectopic endometrial tissue.

Conclusion(s): This constitutes the first report of increased expression of GREB1, as well as cyclin D1 and c-myc, in peritoneal endometriotic lesions, implicating these proteins in estrogen-dependent growth in this context.