Data from Endometrial Carcinomas with <i>POLE</i> Exonuclease Domain Mutations Have a Favorable Prognosis

Abstract

<div>Abstract<p><b>Purpose:</b> The aim of this study was to confirm the prognostic significance of <i>POLE</i> exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on <i>POLE</i>-mutated tumors was assessed.</p><p><b>Experimental Design:</b> A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the <i>POLE</i> exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of <i>POLE</i> 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 HR for PFS, DSS, and OS.</p><p><b>Results:</b><i>POLE</i>EDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with <i>POLE</i>-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, <i>POLE</i>-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, <i>POLE</i> EDM<i>s</i> were only significantly associated with improved PFS. The effect of adjuvant treatment on <i>POLE</i>-mutated cases could not be determined conclusively; however, both treated and untreated patients with <i>POLE</i> EDMs had good outcomes. Meta-analysis revealed an association between <i>POLE</i> EDM<i>s</i> and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15–0.73] and 0.35 (95% CI, 0.13–0.92), respectively.</p><p><b>Conclusions:</b> <i>POLE</i> EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. <i>Clin Cancer Res; 22(12); 2865–73. ©2016 AACR</i>.</p></div>