# Prognostic significance of POLE proofreading mutations in endometrial cancer

Source: https://onco.cc/key-papers/paper-church-pole-endometrial-jnci-2015/  
OnCo record `paper-church-pole-endometrial-jnci-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Endometrial cancers with mutations in the proofreading domain of POLE, though hypermutated and often high grade, almost never recur, identifying a group of women who can be spared adjuvant treatment.

## Summary

Analysis of 788 endometrial cancers from the PORTEC-1 and PORTEC-2 trials for POLE exonuclease domain mutations, found in 6.1 percent, with survival analysis and a meta-analysis of published series.

POLE-mutant tumours were more often high grade yet had excellent recurrence-free survival (hazard ratio 0.14) and cancer-specific survival, independent of other prognostic factors.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: JNCI: Journal of the National Cancer Institute
- Year: 2015
- DOI: 10.1093/jnci/dju402
- Authors: Church DN, Stelloo E, Nout RA, et al.
- Findings: POLE exonuclease domain mutations in 6.1 percent of tumours.; Recurrence-free survival hazard ratio 0.14 for POLE-mutant tumours.
- What it means: POLE sequencing is now part of endometrial cancer classification, and guidelines allow omission of adjuvant therapy for stage I to II POLE-mutated tumours.
- Caveats: Retrospective analysis of trial cohorts; only pathogenic hotspot mutations carry the favourable prognosis.

## Sources

- J Natl Cancer Inst 2015: https://doi.org/10.1093/jnci/dju402
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25505230/

## Connected records

- cancers: [POLE-ultramutated endometrial cancer](https://onco.cc/cancers/endometrial-pole-ultramutated/)
- journals: [JNCI: Journal of the National Cancer Institute](https://onco.cc/journals/jnci/)

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