title: Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies.
abstract: Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.
authors.affiliation: Medical Oncology Unit, Policlinico S.Orsola-Malpighi Hospital, Bologna, Italy. claudio.zamagni@aosp.bo.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: Pierandrea
authors.initials: P
authors.lastname: De Iaco
authors.forename: Marta
authors.initials: M
authors.lastname: Rosati
authors.forename: Elke
authors.initials: E
authors.lastname: Veltrup
authors.forename: Federica
authors.initials: F
authors.lastname: Rosati
authors.forename: Elisa
authors.initials: E
authors.lastname: Capizzi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Cacciari
authors.forename: Carlo
authors.initials: C
authors.lastname: Alboni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bernardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.forename: Sara
authors.initials: S
authors.lastname: Quercia
authors.forename: Antonietta
authors.initials: A
authors.lastname: D'Errico Grigioni
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Andrea Angelo
authors.initials: AA
authors.lastname: Martoni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D016190:Carboplatin; D017239:Paclitaxel