title: Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications.
abstract: This paper aims to validate whether hormone receptor expression is associated with longer survival among women diagnosed with ovarian endometrioid carcinoma (EC), and whether it identifies patients with stage IC/II tumors with excellent outcome that could be spared from toxic chemotherapy. Expression of estrogen receptor (ER) and progesterone receptor (PR) was assessed on 182 EC samples represented on tissue microarrays using the Alberta Ovarian Tumor Type (AOVT) cohort. Statistical analyses were performed to test for associations with ovarian cancer specific survival. ER or PR expression was present in 87.3% and 86.7% of cases, respectively, with co-expression present in 83.0%. Expression of each of the hormonal receptors was significantly higher in low-grade tumors and tumors with squamous differentiation. Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08-0.42,p= 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10-0.53,p= 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease. However, the five-year ovarian cancer specific survival among women with ER positive stage IC/II EC was 89.0% (standard error 3.3%) and for PR positive tumors 89.9% (standard error 3.2%), robustly below the 95% threshold where adjuvant therapy could be avoided. We validated the association of hormone receptor expression with ovarian cancer specific survival independent of standard predictors in an independent sample set of EC. The high ER/PR co-expression frequency and the survival difference support further testing of the efficacy of hormonal therapy in hormone receptor-positive ovarian EC. The clinical utility to identify a group of women diagnosed with EC at stage IC/II that could be spared from adjuvant therapy is limited.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 2T9, Canada. peter.rambau@ucalgary.ca.|Department of Pathology, Catholic University of Health and Allied Sciences, P.O. Box 1464, Mwanza, Tanzania. peter.rambau@ucalgary.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Rambau
authors.affiliation: Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. lkelemen@post.harvard.edu.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. lkelemen@post.harvard.edu.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.affiliation: Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T5H 3V9, Canada. Helen.Steed@albertahealthservices.ca.
authors.forename: Helen
authors.initials: H
authors.lastname: Steed
authors.affiliation: Division of General Surgery and Surgical Oncology, University of Calgary, Calgary, AB T2N 2T9, Canada. MayLynn.Quan@albertahealthservices.ca.
authors.forename: May Lynn
authors.initials: ML
authors.lastname: Quan
authors.affiliation: Department of Gynecological Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 2T9, Canada. Prafull.Ghatage@albertahealthservices.ca.
authors.forename: Prafull
authors.initials: P
authors.lastname: Ghatage
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 2T9, Canada. martin.koebel@cls.ab.ca.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D018269:Carcinoma, Endometrioid / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: endometrioid; estrogen receptor; hormonal therapy; ovarian cancer; progesterone receptor; prognosis