title: Prognostic significance of the estrogen receptor beta (ERβ) isoforms ERβ1, ERβ2, and ERβ5 in advanced serous ovarian cancer.
abstract: OBJECTIVE
  In the present study we have examined the pattern of expression of the full length estrogen receptor β (ERβ1) and two ERβ splice variant isoforms (ERβ2, ERβ5) in well-characterized advanced serous ovarian cancers.
  
  
  METHODS
  Immunohistochemistry was performed with ERβ1, ERβ2, and ERβ5 antibodies and results were correlated with pathological and clinical follow-up data. Expression of ERβ isoforms in a panel of ovarian cancer cell lines and human tumor xenografts was also assessed.
  
  
  RESULTS
  Immunohistochemical staining revealed cellular compartment-specific distribution for each isoform in malignant ovarian tissues exhibiting both nuclear staining and cytoplasmic staining. Patients with cytoplasmic ERβ2 expression had significantly worse outcome (p = 0.006 at the multivariate analysis), the 5-year survival rate being nearly 28% for patients who did express cytoplasmic ERβ2, and 60% in negative patients. Cytoplasmic ERβ2 expression was also found to be significantly associated with chemoresistance. In concordance with clinical results both nuclear and cytoplasmic expressions were observed for the three isoforms in the cancer cell lines and human tumor xenografts tested.
  
  
  CONCLUSIONS
  This is the first study to uncover an unfavorable prognostic role of ERβ2 in advanced serous ovarian cancer. If anomalies of ERβ2 cytoplasmic expression could be demonstrated to represent an independent unfavorable prognostic marker and/or a marker predicting chemoresistance in advanced serous ovarian cancer, its immunohistochemical assessment at the time of surgery, could help to recognize candidates for clinical trials of new interventions.
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciucci
authors.affiliation: Department of Histopathology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Travaglia
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Petrillo
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. Electronic address: d.gallo@rm.unicatt.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D020033:Protein Isoforms; D016019:Survival Analysis
chemical_list: D047629:Estrogen Receptor beta; D020033:Protein Isoforms
keywords: Epithelial ovarian carcinomas; Estrogen; Estrogen receptor beta; Estrogen receptors; Ovary; Survival