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.
Highlights
80% of ovarian endometrioid carcinomas (ECs) present with disease confined to the pelvis [1]
We recently showed in a histotype-specific analysis using a large pooled cohort from the international Ovarian Tumor Tissue Analysis (OTTA) consortium that estrogen receptor (ER) and progesterone receptor (PR) expression was associated with improved survival in EC (n = 484) [13]
This confirms the biological validity of an association of hormone receptor expression status with survival in EC using an independent set of samples “collected at a different point in time, at different institutions, from a different patient population, with samples processed in a different laboratory demonstrating the broad applicability” of this test, which adheres to the recommendation ‘1a’ from the Institute of Medicine on biomarker studies [16]
Summary
80% of ovarian endometrioid carcinomas (ECs) present with disease confined to the pelvis (stage I and II) [1]. EC carries the most favorable prognosis among the ovarian carcinoma histotypes with a five-year survival rate of more than 70% across all stages. For patients diagnosed at sub-stage IA/IB or FIGO (International Federation of Obstetricians and Gynecologists) 2014 IC1 (IC with surgical spill only) the five-year survival is about 95% and those patients do not require adjuvant therapy after surgery [2,3]. Despite an excessive amount of literature on prognostic markers in ovarian carcinoma in general, none are in clinical use. Many of the formerly diagnosed “high-grade endometrioid” carcinomas are classified as high-grade serous carcinoma, which is supported by molecular evidence (e.g., combination of WT1 expression with TP53 mutation or BRCA1/2 mutations) [7,8,9,10]. Contemporarily classified retrospective EC cohorts are sparse
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