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.