971 Mismatch-repair deficiency is associated with a higher risk of recurrence than no specific molecular profile in early-stage endometrial cancer

Introduction/Background The prognostic significance of MMR deficiency (MMRd) has not been unequivocally established yet. Thus, treatment recommendations for newly diagnosed early MMRd EC patients do not differ from those with no specific molecular profile (NSMP). As a part of our research project concerning EC, this study aimed to assess the prognostic significance of MMR status and to compare clinical outcomes between MMRd and NSMP cohorts (defined as those with MMR-proficient and non-POLE ultra-mutated, TP53-wild type tumors). Methodology Two cohorts of patients with EC of different clinical behaviors despite an identical initial prognosis (those with recurrence and those in remission for at least 36 months) were consecutively identified from the clinical databases. Molecular testing was performed using immunohistochemistry (IHC) for MMR and next-generation sequencing (NGS) for POLE and TP53 status. The prognostic significance of MMR status was measured by disease-free survival (DSF) using the Kaplan-Meier method and log-rank test. The Cox proportional hazards model estimated the association between MMRd and recurrence expressed as hazard ratio (HR). Results A total of 107 patients with newly diagnosed early-stage EC (n=59 FIGO IA, n=29 FIGO IB, and n=19 FIGO II) were enrolled with n=55 (51%) LG endometrioid, n=33 (31%) HG endometrioid, and n=19 (18%) non-endometrioid carcinoma. The results of molecular testing revealed n=1 (1%) POLE-ultra-mutated, n=42 (39%) MMR-deficient, n=45 (42%) TP53-mutated, and n=19 (18%) NSMP tumor types. In the whole cohort (n=107), MMR deficiency was associated with shorter DFS than MMR proficiency (adjHR 1.9 1.06–3.39, p=0.03; Figure A). When comparing MMR-deficient and NSMP cohorts (n=61), patients with MMR-deficient tumors had a higher risk of recurrence (adjHR 3.58 1.46–8.78, p=0.005; Figure B). Conclusion In this retrospective study, mismatch-repair deficiency was associated with a higher recurrence rate than mismatch-repair proficiency. Patients with MMR-deficient tumors had significantly shorter disease-free survival than those with non-specific molecular profiles. Disclosures This research was funded by the Ministry of Health of the Czech Republic (MHCR), grant number NU21–09-00031.