title: Endometrial Carcinomas with POLE Exonuclease Domain Mutations Have a Favorable Prognosis.
abstract: The aim of this study was to confirm the prognostic significance of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. In addition, the effect of treatment on POLE-mutated tumors was assessed.
  
  
  
  A retrospective patient cohort of 496 endometrial carcinoma patients was identified for targeted sequencing of the POLE exonuclease domain, yielding 406 evaluable tumors. Univariable and multivariable analyses were performed to determine the effect of POLE mutation status on progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). Combining results from eight studies in a meta-analysis, we computed pooled HR for PFS, DSS, and OS.
  
  
  
  POLE EDMs were identified in 39 of 406 (9.6%) endometrial carcinomas. Women with POLE-mutated endometrial carcinomas were younger, with stage I (92%) tumors, grade 3 (62%), endometrioid histology (82%), and frequent (49%) lymphovascular invasion. In univariable analysis, POLE-mutated endometrial carcinomas had significantly improved outcomes compared with patients with no EDMs for PFS, DSS, and OS. In multivariable analysis, POLE EDMs were only significantly associated with improved PFS. The effect of adjuvant treatment on POLE-mutated cases could not be determined conclusively; however, both treated and untreated patients with POLE EDMs had good outcomes. Meta-analysis revealed an association between POLE EDMs and improved PFS and DSS with pooled HRs 0.34 [95% confidence interval (CI), 0.15-0.73] and 0.35 (95% CI, 0.13-0.92), respectively.
  
  
  
  POLE EDMs are prognostic markers associated with excellent outcomes for endometrial carcinoma patients. Further investigation is needed to conclusively determine if treatment is necessary for this group of women. Clin Cancer Res; 22(12); 2865-73. ©2016 AACR.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital; and BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital; and BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Aline
authors.initials: A
authors.lastname: Talhouk
authors.affiliation: Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Leung
authors.affiliation: Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: Chiu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital; and BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Winnie
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital; and BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Janine
authors.initials: J
authors.lastname: Senz
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Reha-Krantz
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital; and BC Cancer Agency, Vancouver, British Columbia, Canada. Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada. Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver General Hospital; and BC Cancer Agency, Vancouver, British Columbia, Canada. Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada. jessica.mcalpine@vch.ca.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004257:DNA Polymerase II / Q000235:genetics*; D018572:Disease-Free Survival; D004717:Endometrium / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D000075223:Poly-ADP-Ribose Binding Proteins / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D000075223:Poly-ADP-Ribose Binding Proteins; D004257:DNA Polymerase II; C119525:POLE protein, human