Endometrial carcinomas with POLE exonuclease domain mutations have a favorable prognosis

Purpose: The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma (EC) patients. In addition, the effect of treatment on POLE mutated tumours was assessed. Experimental design: A retrospective patient cohort of 496 EC patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumours. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled hazard ratios (HR) for PFS, DSS, and OS. Results: POLE EDMs were identified in 39 of 406 (9.6%) ECs. Women with POLE mutated ECs were younger, with Stage 1 (92%) tumors, grade 3 (62%), endometrioid histology (82%) and frequent (49%) lymphovascular invasion. In univariable analysis, POLE mutated ECs had significantly improved outcomes compared to patients with no EDMs for PFS, DSS and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE mutated cases could not be determined conclusively, however both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 (95% CI 0.15-0.73) and 0.35 (95% CI 0.13-0.92), respectively. Conclusions: POLE EDMs are prognostic markers associated with excellent outcomes for EC patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women.

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