Hormone receptor expression patterns define clinically meaningful subgroups of endometrioid ovarian carcinoma

Robert L Hollis,Barbara Stanley,Yasushi Iida,John Thomson,Michael Churchman,Tzyvia Rye,Melanie Mackean,Fiona Nussey,Charlie Gourley,C Simon Herrington

doi:10.1016/j.ygyno.2019.09.001

Abstract

BackgroundNumerous studies have investigated the association between hormone receptor expression and clinical outcome in ovarian carcinoma (OC); however, these have largely focussed on serous OCs, with few studies reporting specifically on endometrioid OCs (EnOC). Where analyses have been stratified by histotype, expression has been assessed using the percentage of positive tumor cells, without accounting for nuclear expression intensity. MethodsHere we assess the expression levels of progesterone receptor (PR), estrogen receptor alpha (ER) and androgen receptor (AR) using histoscore – a nuclear scoring method incorporating both proportion of positive cells and the intensity of nuclear staining – across a cohort of 107 WT1 negative EnOCs. ResultsHierarchical clustering by PR, ER and AR histoscores identified four EnOC subgroups (PR+/ER+, PR+/ER−, PR−/ER+ and PR−/ER−). EnOC patients in the PR+/ER+ and PR+/ER− groups displayed favorable outcome (multivariable HR for disease-specific survival 0.05 [0.01–0.35] and 0.05 [0.00–0.51]) compared to the PR−/ER+ group. Ten-year survival for stage II PRhigh and PRlow cases was 94.1% and 42.4%. ERhigh EnOC patients (PR+/ER+, PR−/ER+) had higher body mass index compared to ERlow cases (P = 0.015) and high grade serous OC patients (P < 0.001). ConclusionThese data demonstrate that endometrioid OC cases with high PR expression display markedly favorable outcome. Stage II EnOCs with high PR expression represent potential candidates for de-escalation of first-line therapy. Future work should seek to characterise the sensitivity of PR and ER positive EnOCs to endocrine therapy.

Highlights

Ovarian cancer is the most lethal cancer of the female genital tract, and accounts for over 180,000 deaths per year worldwide [1].The vast majority of cases are ovarian carcinomas (OCs), comprising five core histological subtypes: high grade serous (HGS), endometrioid, clear cell, low grade serous (LGS) and mucinous OC [2].R.L
Higher Body mass index (BMI) is known to be associated with increased risk of endometrial cancer, the majority of which display endometrioid histology and are considered hormone-driven [31]. These data add to the growing evidence that hormone receptors represent clinically meaningful biomarkers of patient outcome in OC
Optimal first-line management strategies for patients with PRhigh endometrioid OCs (EnOC) e who appear to experience exceptional long-term survival e may warrant re-evaluation, in the context of patients diagnosed with stage II disease who would typically undergo systemic chemotherapy [32]

Summary

Introduction

Ovarian cancer is the most lethal cancer of the female genital tract, and accounts for over 180,000 deaths per year worldwide [1].The vast majority of cases are ovarian carcinomas (OCs), comprising five core histological subtypes: high grade serous (HGS), endometrioid, clear cell, low grade serous (LGS) and mucinous OC [2].R.L. The vast majority of cases are ovarian carcinomas (OCs), comprising five core histological subtypes: high grade serous (HGS), endometrioid, clear cell, low grade serous (LGS) and mucinous OC [2]. Reports of the prognostic impact of hormone receptor expression in OC have largely focussed on serous cases, with studies almost ubiquitously focusing on either these tumors alone [8e11], or mixed patient populations dominated by OCs of serous histology [12e17]. Mixed histology studies interrogating survival without stratifying by histological subtype have the potential to be confounded by the known differential expression of hormone receptors across these subtypes [6,18], which are recognised to demonstrate markedly distinct clinical outcome [3,4]. Numerous studies have investigated the association between hormone receptor expression and clinical outcome in ovarian carcinoma (OC); these have largely focussed on serous OCs, with few studies reporting on endometrioid OCs (EnOC). Where analyses have been stratified by histotype, expression has been assessed using the percentage of positive tumor cells, without accounting for nuclear expression intensity

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Results

Discussion

Conclusion