title: Cytoplasmic expression of estrogen receptor beta (ERβ) predicts poor clinical outcome in advanced serous ovarian cancer.
abstract: OBJECTIVE
  In this study we investigated the prognostic value of estrogen receptor α (ERα), ERβ and progesterone receptor (PR) expression in 58 untreated advanced serous ovarian cancer patients. The study also included 12 macroscopically and histopathologically normal ovaries.
  
  
  METHODS
  Protein expression was evaluated by immunohistochemistry, and antibody staining detected in both the nuclear and cytoplasmic compartments was taken into account. Immunopositivity was analyzed in relation to tumor clinicopathological variables, disease-free survival (DFS), and overall survival (OS).
  
  
  RESULTS
  Epithelial cells in ovarian cancer tissue showed significantly lower levels of nuclear ERβ and PR, but not ERα, than in normal ovarian tissue. In the case of ERβ, however, while normal ovarian epithelium exhibited almost exclusively strong nuclear staining, ovarian cancer tissue mostly showed cytoplasmic immunopositivity. Nuclear ERα and ERβ expression were not associated with clinical outcome. Conversely, any cytoplasmic ERβ expression was an independent unfavorable prognostic factor for DFS, a finding approaching statistical significance also for OS. These data suggest that, in advanced serous ovarian cancer, cytoplasmic ERβ 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.
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: De Stefano
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Prisco
authors.forename: Anna
authors.initials: A
authors.lastname: Fagotti
authors.forename: Lucia
authors.initials: L
authors.lastname: Tortorella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vizzielli
authors.forename: Luca
authors.initials: L
authors.lastname: Mencaglia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011980:Receptors, Progesterone / Q000096:biosynthesis
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011980:Receptors, Progesterone; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin