Most patients present with low-grade (grade 1-2) early-stage (FIGO I-II) endometrioid EC (EEC), it is questioned whether these patients benefit from molecular profiling. We aim to investigate the prognostic relevance of molecular profiling within low-grade EEC.
A retrospective multicenter study within the European Network for Individualized Treatment (ENITEC) network. Patients with early-stage EC were excluded if lymph node status was unknown. Molecular profiling was conducted using single-molecule Molecular Inversion Probes based on Next Generation Sequencing. Subsequently, cases were classified as: polymerase epsilon (POLE) mutant, microsatellite instable (MSI), tumor protein (TP53) mutation and no-specific molecular profile (NSMP).
Total of 393 EC patients were included, 75% had early-stage EC, and 54% low-grade EEC. Of all patients, 8.1% was classified as POLEmut, 16.8% as MSI, 21.4% as TP53-mutated and 53.7% as NSMP. Median follow-up was 5.3-years. Across all molecular subgroups, patients with low-grade EEC had superior disease-specific survival (DSS) compared to high-grade (grade 3) EC, respectively >89% vs. >43%. Equally, patients with low-grade EEC had improved recurrence-free survival (RFS) compared to high-grade EC within POLEmut, MSI and NSMP. Within TP53-mutated, only grade 1 EEC showed an excellent RFS (92%) when compared to grade 2 (54%) and grade 3 EC (44%). In multivariate analysis that included age, lymphovascular space invasion, grade, FIGO stage and the four molecular subgroups, TP53-mutated, high-grade and advanced-stage (FIGO III-IV) remained independent prognostic factors for reduced DSS and RFS (respectively, hazard ratio (HR) 9.20 (95%-CI 1.23-68.90) p=0.031, HR 5.91 (95%-CI 2.63-13.28) p<0.001, HR 3.02 (95%-CI 1.61-5.62) p<0.001 and respectively, HR 12.27 (95%-CI 1.66-90.78) p=0.014, HR 2.66 (95%-CI 1.54-4.57) p<0.001, HR 2.58 (95%-CI 1.56-4.24) p<0.001).
Patients with grade 1 EEC have an excellent prognostic outcome across all molecular subgroups. In patients with grade 2 EEC, TP53-mutated seems to be prognostic relevant. Based on current data, routine molecular profiling in patients with low-grade EEC has shown limited contributive value to prognostic outcome.
The authors.
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All authors have declared no conflicts of interest.