Cytoplasmic expression of estrogen receptor beta (ERβ) predicts poor clinical outcome in advanced serous ovarian cancer

Objective. In this study we investigated the prognostic value of estrogen receptor alpha (ER alpha). ER beta and progesterone receptor (PR) expression in 58 untreated advanced serous ovarian cancer patients. The study also included 12 macroscopically and histopathologically normal ovaries. Materials and Methods. Protein expression was evaluated by immunohistochemistry, and antibody staining detected in both the nuclear and cytoplasmic compartments was taken into account. lmmunopositivity was analyzed in relation to tumor chnicopathological variables. disease-free survival (DFS), and overall survival (OS). Results. Epithelial cells in ovarian cancer tissue showed significantly lower levels of nuclear ER beta and PR, but not ER alpha, than in normal ovarian tissue. In the case of ER beta, however, while normal ovarian epithelium exhibited almost exclusively strong nuclear staining, ovarian cancer tissue mostly showed cytoplasmic immunopositivity. Nuclear ER alpha and ER beta expression were not associated with clinical outcome. Conversely, any cytoplasmic ER beta expression was an independent unfavorable prognostic factor for DES, a finding approaching statistical significance also for OS. These data suggest that, in advanced serous ovarian cancer, cytoplasmic ER beta signaling may be more important for patient survival than its nuclear signaling. In the case of PR, positivity was an independent favorable prognostic factor for DFS. Conclusions. These novel findings, that need to be confirmed in a large prospective trial, suggest that additional prognostic, and possibly therapeutic opportunities may be available in advanced serous ovarian cancer. (C) 2011 Elsevier Inc. All rights reserved.