期刊
GYNECOLOGIC ONCOLOGY
卷 134, 期 1, 页码 15-19出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2014.05.006
关键词
Endometrial cancer; Endometrioid; POLE; Prognosis
资金
- University of Alberta [RES0019506]
- Calgary Laboratory Services Internal Research Competition fund [RS10-536]
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. (C) 2014 Elsevier Inc. All rights reserved.
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