POLE Proofreading Mutations Predict Better Outcome in Endometrial Cancer

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In a study reported in the Journal of the National Cancer Institute, Church and colleagues assessed whether proofreading mutations in POLE (which encodes the DNA polymerase epsilon catalytic subunit) were associated with prognosis in endometrial cancer. Such mutations have been reported in approximately 7% of endometrial cancers.

Targeted POLE sequencing in 788 patients from the PORTEC-1 and -2 trials identified mutations in 48 of them (6.1%), with the presence of mutation being associated with a high tumor grade (P < .001). Patients with mutations had a lower frequency of tumor recurrence (6.2% vs 14.1%) and endometrial cancer death (2.3% vs 9.7%).

In the total cohort, the reductions in recurrence-free survival (hazard ratio [HR] = 0.43, P = .15) and cancer-specific survival (HR = 0.19, P = .11) were not significant on multivariate analysis. However, among 109 patients with grade 3 tumors, tumor recurrence was observed in 0 of 15 patients with POLE-mutant disease vs 29 of the 94 (30.9%) with wild-type cancers, with recurrence-free survival being significantly improved on multivariate analysis (HR = 0.11, P = .03).

In an additional series of 628 patients, endometrial cancer–related events occurred in 0 of 33 patients with POLE-mutant disease. For the pooled cohorts, patients with POLE-mutant disease had significantly improved recurrence free-survival (HR = 0.33, P = .03), with an improvement approaching significance in cancer-specific survival (HR = 0.26, P = .06).

The investigators concluded: “POLE proofreading mutations predict favorable [endometrial cancer] prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in [endometrial cancer].” ■

Church DN, et al: J Natl Cancer Inst 107:402, 2014 (print January 2015).




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