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

ABSTRACT: BACKGROUND:Numerous 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. METHODS:Here 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. RESULTS:Hierarchical 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?

SUBMITTER: Hollis RL

PROVIDER: S-EPMC6854467 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Hollis Robert L RL Stanley Barbara B Iida Yasushi Y Thomson John J Churchman Michael M Rye Tzyvia T Mackean Melanie M Nussey Fiona F Gourley Charlie C Herrington C Simon CS

Gynecologic oncology 20190905 2

<h4>Background</h4>Numerous 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.<h4>Methods</h4>Here we assess the expression lev ...[more]

PMID: 31495455

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Project description:Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER-) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR-/ER + , PR-/ER-) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04-0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14-5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours-which are typically CTNNB1-mutant and TP53 wild-type-experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.

Dataset Information

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

Publications

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

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