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Prognostic Significance of POLE Exonuclease Domain Mutations in High-Grade Endometrioid Endometrial Cancer on Survival and Recurrence: A Subanalysis
  1. Caroline C. Billingsley, MD,
  2. David E. Cohn, MD,
  3. David G. Mutch, MD,
  4. Erinn M. Hade, PhD and
  5. Paul J. Goodfellow, PhD
  1. * Division of Gynecology Oncology, Department of Obstetrics and Gynecology, The Ohio State University, College of Medicine, Columbus, OH;
  2. Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Washington University, St Louis, MO; and
  3. Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH.
  1. Address correspondence and reprint requests to Caroline C. Billingsley, MD, Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, The Ohio State University, M210 Starling Loving, 320 W 10th Ave, Columbus, OH 43210. E-mail: caroline.billingsley{at}


Objective POLE mutations in high-grade endometrioid endometrial cancer (EEC) have been associated with improved survival. We sought to investigate the prevalence of POLE tumor mutation and its prognostic significance on outcomes and clinical applications in a subanalysis of women with high-grade EEC from a previously described cohort of 544 EEC patients in which POLE mutation status and survival outcomes were assessed.

Methods Polymerase chain reaction amplification and Sanger sequencing were used to test for POLE mutations in 72 tumors. Associations between POLE mutation, demographic and clinicopathologic features, and survival were investigated with Cox proportional hazard models.

Results POLE mutations were identified in 7 (9.7%) of 72 grade 3 EECs. No significant differences in the clinicopathologic features between those with POLE mutations and those without were identified. Adjusted for age, a decreased risk of recurrence was suggested in patients with a POLE mutation (adjusted hazard ratio, 0.37; 95% confidence interval, 0.09–1.55), as well as decreased risk of death (adjusted hazard ratio, 0.19; 95% confidence interval, 0.03–1.42).

Conclusions POLE mutations in tumors of women with grade 3 EEC are associated with a lower risk of recurrence and death, although not statistically significant because of high variability in these estimates. These findings, consistent with recently published combined analyses, support POLE mutation status as a noteworthy prognostic marker and may favor a change in the treatment of women with grade 3 EECs, particularly in those with early-stage disease, in which omission of adjuvant therapy and decreased surveillance could possibly be appropriate.

  • Endometrial cancer
  • High-grade
  • POLE mutation
  • Prognostic marker

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  • The authors declare no conflicts of interest.