The prognostic relevance of estrogen (ER) and progesterone receptor (PR) expression in endometrioid endometrial cancer is still controversially discussed. The present study has focused on the evaluation of the prognostic value of ERα, ERβ1, ERβ2, and PR in this histotype. Specifically, we were interested in evaluating whether the relative level of ER subtype-specific expression (in terms of a ratio ERα/ERβ1 and ERα/ERβ2) would predict clinical outcome better than their absolute levels in patients with endometrioid endometrial cancer. To this end, protein content was assessed by immunohistochemistry in a group of 121 cases and staining was analyzed in relation to clinicopathologic variables, disease-free survival and overall survival. Results obtained have demonstrated that none of the biological markers analyzed possess an independent prognostic role with regard to disease-free survival. Multivariate analysis of overall survival has shown that ERα alone is not an independent prognostic indicator in patients with endometrioid endometrial cancer (hazard ratio [HR]; 0.5; 95% confidence interval [CI], 0.09-3.0; P = .5). On the other hand, an ERα/ERβ1 ratio of 1 or less or an ERα/ERβ2 ratio of 1 or less has proved to be independently associated with a higher risk of death (HR, 6.4 [95% CI, 1.0-40.6; P = .04] and 9.7 [95% CI, 1.1-85.3; P = .04], respectively) along with age, tumor stage, and Ki-67. In conclusion, we report here that the ERα/ERβ1 and ERα/ERβ2 expression ratios are independent prognostic markers of survival in endometrioid endometrial cancer; these findings suggest that phenotyping these interacting markers conjointly may better predict patient survival than each individual marker alone.
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