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Prognostic and theragnostic biomarkers in ovarian clear cell carcinoma.

By Katharina Wiedemeyer, Linyuan Wang, Eun Young Kang, Shuhong Liu, Young Ou, Linda E. Kelemen, Lukas Feil, Michael S Anglesio, Sarah Glaze, Prafull Ghatage, Gregg S Nelson, Martin Kobel

Posted 24 Aug 2020
medRxiv DOI: 10.1101/2020.08.21.20178830

In this study, we aimed to test whether prognostic biomarkers can achieve a clinically relevant stratification of patients with stage I ovarian clear cell carcinoma (OCCC) and to survey the expression of 10 selected actionable targets (theragnostic biomarkers) in stage II to IV cases. From the population-based Alberta Ovarian Tumor Type study, 160 samples of OCCC were evaluated by immunohistochemistry and/or silver-enhanced in-situ hybridization for the status of 5 prognostic (p53, p16, IGF2BP3, CCNE1, FOLR1) and 10 theragnostic biomarkers (ALK, BRAF, ERBB2, ER, MET, MMR, PR, ROS1, NTRK1-3, VEGFR2). Kaplan-Meier survival analyses were performed. Cases with abnormal p53 or combined p16/IFG2BP3 abnormal expression identified a small subset of patients (6/54 cases) with stage I OCCC with an aggressive course (5-year ovarian cancer specific survival of 33.3%, compared to 91.5% in the other stage I cases). Among theragnostic targets, ERBB2 amplification was present in 11/158 (7%) of OCCC, while MET was ubiquitously expressed in OCCC similar to a variety of normal control tissues. ER/PR showed a low prevalence of expression. No abnormal expression was detected for any of the other targets. We propose a combination of 3 biomarkers (p53, p16, IGF2BP3) to predict prognosis and the potential need for adjuvant therapy for patients with stage I OCCC. This finding requires replication in larger cohorts. Additionally, OCCC could be tested for ERBB2 amplification for inclusion in gynecological basket trials targeting this alteration.

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