Abstract 322: High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with superior survival and platinum sensitivity

Abstract

Abstract EMSY, encoding a BRCA2-binding protein, is reportedly amplified in 6-18% of high grade serous ovarian carcinomas (HGSOCs). As a negative regulator of BRCA2, HGSOCs with EMSY overexpression may mimic BRCA-mutant patients, who experience superior clinical outcome and hypersensitivity to platinum chemotherapy and PARP inhibition by virtue of homologous recombination deficiency (HRD). Here we investigate the impact of EMSY expression, extracted from local and publicly available transcriptomic data, on the outcome and platinum sensitivity of HGSOCs. Platinum response data were collected from the Edinburgh Ovarian Cancer Database. Overall survival (OS) and progression-free survival (PFS) differences were assessed using multivariate cox regression accounting for age, stage at diagnosis and debulking status. Within the Edinburgh cohort, high EMSY expression was associated with superior OS and PFS (table 1). Datasets from the MRC ICON7 trial control arm, Tothill et al, Mateescu et al, Pils et al, and TCGA cohorts demonstrated similar benefit for high-EMSY patients. Within the Edinburgh cohort, high-EMSY patients displayed significantly superior complete response (CR) rate to platinum at second (radio CR 44.4% vs 12.5%, P = 0.035; CA125 CR 88.0% vs 55.0%, P = 0.002) and third exposure (radio CR 50.0% vs 5.9%, P = 0.080; CA125 CR 53.3% vs 21.3%, P = 0.021), with prolonged time to progression (median 127 vs 83.5 days from second platinum, P = 0.084; median 151.5 vs 60.5 days from third platinum, P = 0.004). Within high-risk (advanced stage suboptimally debulked) HGSOCs, more high-EMSY patients remained recurrence-free 5 and 10 years from diagnosis (17.6% vs 2.7%, P = 0.031; 12.5% vs 0.9%, P = 0.041). Together these data demonstrate a subgroup of HGSOCs defined by high EMSY expression experience superior clinical outcome and platinum sensitivity, consistent with HRD. This subgroup may therefore represent HGSOCs that are also sensitive to PARP inhibition. DatasetEventMulti HR95% CIPEdinburghOS0.590.39 – 0.900.013PFS0.600.38 – 0.930.022MRC ICON7 control armOS0.210.07 – 0.680.009Tothill (primary tumour masses)OS0.280.09 – 0.900.032MateescuOS0.430.18 – 0.990.048PilsOS0.270.08 – 0.870.028TCGA advanced stage patientsPFS0.690.45 – 1.050.081 Citation Format: Robert L. Hollis, Michael Churchman, Tzyvia Rye, Andrena M. McCavigan, Laura A. Knight, Richard Kennedy, C. Simon Herrington, Charlie Gourley. High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with superior survival and platinum sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 322.