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Prognostic significance of POLE proofreading mutations in endometrial cancer.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 2014 Dec 12; Vol. 107 (1), pp. 402. Date of Electronic Publication: 2014 Dec 12 (Print Publication: 2015). - Publication Year :
- 2014
-
Abstract
- Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis.<br />Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided.<br />Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06).<br />Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC.<br /> (© The Author 2014. Published by Oxford University Press.)
- Subjects :
- Adult
Disease-Free Survival
Endometrial Neoplasms pathology
Female
Humans
Kaplan-Meier Estimate
Neoplasm Grading
Odds Ratio
Poly-ADP-Ribose Binding Proteins
Predictive Value of Tests
Prognosis
Biomarkers, Tumor genetics
DNA Polymerase II genetics
Endometrial Neoplasms genetics
Endometrial Neoplasms mortality
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2105
- Volume :
- 107
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 25505230
- Full Text :
- https://doi.org/10.1093/jnci/dju402