Analysis of the expression of estrogen receptor, progesterone receptor and chicken ovalbumin upstream promoter-transcription factor I in ovarian epithelial cancers and normal ovaries

Abstract

Sex hormones are involved in the carcinogenesis of some gynecologic cancers, and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 diagnosed as malignant epithelial neoplasms (group A), 45 as benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (p=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (p=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (p=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor <1 cm as the most significant clinical prognostic factor in group A (p=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.