title: Hormone receptor expression profile of low-grade serous ovarian cancers.
abstract: Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments.
  
  
  
  Estrogen receptor α (ERα), ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) expression was evaluated by immunohistochemistry in 25 untreated LGSOC primary tumors, 6 matched metastases and 6 micropapillary variant of serous borderline tumors (micropapillary SBOTs). In vitro cellular models were used to provide insights into clinical observations.
  
  
  
  Our results showed prominent expression of nuclear ERα, ERβ2, ERβ5 and PR in LGSOC primary tissues, while metastatic lesions also exhibit considerable cytoplasmic ERβ2 levels. Notably, a higher expression of ERβ1 protein was determined in micropapillary SBOTs compared to LGSOCs. In vitro experiments on LGSOC cell lines (i.e. HOC-7 and VOA-1056) revealed low/absent ERα, PR and AR protein expression, whereas the three ERβ isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands.
  
  
  
  These novel findings highlight the need of assessing relative levels of ERα and ERβ isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC.
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Buttarelli
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Mascilini
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciucci
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinelli
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Filippetti
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; Department of Health Sciences and Medicine, University of Molise, Campobasso, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Unit of Translational Medicine for Women and Children Health, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. Electronic address: daniela.gallo@unicatt.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D047629:Estrogen Receptor beta / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms; D011944:Receptors, Androgen / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C410798:AR protein, human; C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D011944:Receptors, Androgen; D011980:Receptors, Progesterone
keywords: Borderline ovarian tumor; ERα; ERβ; Estradiol; Hormonal therapy; Ovary