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Gynecol Oncol. 2014 Jul;134(1):15-9. doi: 10.1016/j.ygyno.2014.05.006. Epub 2014 May 16.

POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium.

Author information

1
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
2
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
3
Department of Oncology, University of Calgary and Translational Laboratory, Tom Baker Cancer Centre, Calgary, AB, Canada.
4
Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada.
5
Department of Gynecologic Oncology, Tom Baker Cancer Centre and University of Calgary, Calgary, AB, Canada.
6
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada. Electronic address: chlee2@ualberta.ca.

Abstract

OBJECTIVE:

POLE exonuclease domain mutations were recently found to occur in a subset of endometrial carcinomas and result in defective proof-reading function during DNA replication. The aim of this study is to further characterize the clinical and pathologic significance of POLE exonuclease domain mutations in high-grade endometrial carcinomas.

METHODS:

We assessed for mutations in the exonuclease domain of POLE by Sanger sequencing in 53 grade 3 endometrioid, 25 serous, 16 clear cell and 5 dedifferentiated carcinomas. We correlated POLE mutation status with clinicopathologic features and molecular parameters. Univariate and multivariate survival analyses were performed using Kaplan-Meier and cox regression analyses.

RESULTS:

POLE exonuclease domain mutations were identified in 8 of 53 (15%) grade 3 endometrioid carcinomas and not in any other histotypes examined. Only 1 of the 8 grade 3 endometrioid carcinomas with POLE exonuclease domain mutation displayed deficient mismatch repair protein expression by immunohistochemistry (MSH6 loss), compared to 21 of 45 grade 3 endometrioid carcinomas with wild-type exonuclease domain. When analyzed together with published grade 3 endometrioid carcinomas by The Cancer Genome Atlas, the presence of POLE exonuclease domain mutation was associated with significantly better progression-free survival in univariate (p=0.025) and multivariate (p=0.010) analyses, such that none of the patients with POLE mutated tumors experienced disease progression

CONCLUSIONS:

POLE exonuclease domain mutations occur in a subset of grade 3 endometrioid carcinomas and are associated with good clinical outcome. It can serve as an important prognostic molecular marker to guide the management of patients with grade 3 endometrioid carcinomas.

KEYWORDS:

Endometrial cancer; Endometrioid; POLE; Prognosis

PMID:
24844595
DOI:
10.1016/j.ygyno.2014.05.006
[Indexed for MEDLINE]

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