1. Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile
- Author
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Jesus Gonzalez-Bosquet, S. John Weroha, Jamie N. Bakkum-Gamez, Amy L. Weaver, Michaela E. McGree, Sean C. Dowdy, Abimbola O. Famuyide, Benjamin R. Kipp, Kevin C. Halling, Siddhartha Yadav, Fergus J. Couch, and Karl C. Podratz
- Subjects
CCNA2 ,ECPPF ,E2F1 ,endometrial cancer ,FBXW7 ,MSI ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectiveTo identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.MethodsWe searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.ResultsData were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P
- Published
- 2023
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