O015/#502 Molecular stratification of ovarian clear cell carcinoma predicts clinical outcomes. (4th December 2022)

• Record Type: Journal Article
• Authors: Gordhandas, Sushmita; Manning-Geist, Beryl; Hodgson, Anjelica; Zhou, Qin; Iasonos, Alexia; Chi, Dennis; Momeni-Boroujeni, Amir; Abu-Rustum, Nadeem; Leitao, Mario; Long Roche, Kara; Sonoda, Yukio; Aghajanian, Carol; Alektiar, Khaled; Grisham, Rachel; Zivanovic, Oliver; Ellenson, Lora; Weigelt, Britta
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 3
• Page Start: A9
• Page End: A9
• Publication Date: 2022-12-04
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-igcs.17
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objectives: We sought to investigate if molecular profiles and endometrial cancer (EC)-based molecular subtyping are associated with clinicopathologic variables and outcomes in ovarian clear cell carcinomas (OCCCs). Methods: Patients with OCCC who underwent clinical panel-based sequencing from 4/2015–1/2021 were identified. Pathogenic somatic alterations, EC molecular subtypes, clinicopathologic variables, and survival outcomes were obtained. Appropriate statistical methods were applied. Results: Following central pathology review, 119 OCCCs were identified. Stage at diagnosis was equally distributed (54% I/II; 46% III/IV). Eighty-three percent (n=99) were copy number (CN)-low, 12% (n=14) were CN-high, 4% (n=5) were microsatellite instability (MSI)-high, and 1% (n=1) were POLE mutated. The most frequent genetic alterations were ARID1A (n=80, 67%), PIK3CA (n=56, 47%), TERT promoter (n=27, 23%), and PPP2R1A (n=19, 16%). ARID1A and TERT alterations were mutually exclusive (p=0.04, q=0.19). Endometriosis was significantly enriched in CN-low OCCCs (p=0.02), and patients diagnosed at <50 years of age were more likely to harbor PIK3CA alterations (p=0.04). In the entire cohort, multivariate analysis of outcome revealed that Asian race (p=0.04), advanced stage (p<0.01), and CN-high subtype (p=0.03) were significantly associated with worse progression-free survival; advanced stage (p=0.01) and PPP2R1A alterations (p=0.04) were significantly associated with worse overall survival. Univariate sensitivity analysis including only patients who had the initial treatment planning at our institution found the same survival associations. Conclusions: OCCC is a heterogenous group of tumors with varied clinical outcomes and molecular profiles. In this retrospective series of OCCCs, race, EC-based molecular subtype, stage at diagnosis, and PPP2R1A alterations were predictive of outcome.