Refining prognosis of Endometrioid Ovarian Carcinoma subtypes using hormone receptors expression
Bianca Ribeiro de Souza1, Karolin Heinze1, Andrea Neilson1, Janine Senz2, Evan S Cairns1, Charlotte Meyer3, Derek S Chiu1, Samuel CY Leung1, Marcel Grube3,4, Stefan Kommoss3,4, Martin Köbel5, Michael S Anglesio1,2.
1Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; 2Department of Pathology and Lab Medicine, University of British Columbia, Vancouver, BC, Canada; 3Department of Women's Health, University of Tübingen, Tübingen, Germany; 4Department of Obstetrics and Gynecology, Diakonie-Klinikum, Schwäbisch Hall , Germany; 5Department of Pathology, University of Calgary, Calgary, AB, Canada
Introduction Endometrioid Ovarian Carcinoma (ENOC) is an under-investigated ovarian cancer type that often affects pre-menopausal women and is associated with endometriosis. Most ENOC patients (70%) fall into a heterogeneous subtype called no specific molecular profile (NSMP). Past ENOC studies are based on small cohorts and confounded by histotyping inaccuracies. We investigated the prognostic value of estrogen receptor (ER), progesterone receptor (PR), and β-catenin (CTNNB1) among ENOC and within NSMP.
Methods We assembled a series of 620 ENOC cases from nine cohorts across four countries. Using Kaplan-Meier method and Cox's models, we assessed the association of overall (OS), disease-specific (DSS), and progression-free survival (PFS) with ER, PR, and CTNNB1 immunohistochemistry data.
Results ER+, PR+ (and the dual positivity) were associated with improved survival outcomes for both ENOC (P<0.001) and the NSMP subtype (P≤0.01) in univariate analysis. Multivariable analysis including age, stage, and grade confirmed prognostic association of ER+ (P=0.01), PR+ (P=0.004), and ER+/PR+ (P=0.001) in ENOC, while in NSMP they remained significant for PFS only (P≤0.02). CTNNB1 positivity was associated with improved survival in the full ENOC cohort (P<0.05) but with modest effect in univariable analysis.
Conclusion Taken together, the presence of dual positivity ER/PR displayed the most favorable outcome in both ENOC (DSS HR 0.34 [95% CI 0.2–0.5] P<0.001) and NSMP (DSS HR 0.37 [0.2–0.7] P=0.001), compared to all other biomarker combinations (ER+/PR-, ER-/PR+, ER-/PR-), regardless of CTNNB1. The clear separation of prognosis in this large cohort supports further risk stratification, especially within NSMP. More work is needed to identify targetable features in hormone receptor-negative NSMP. Hormone receptor targeting may be more favorable than traditional platinum-based chemotherapies in ER+/PR+ NSMP however loss of receptor status at recurrence requires monitoring.