title: Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer.
abstract: Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs.
  
  
  
  Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples. Subgroups were characterized and assessed relative to outcomes. The prognostic ability of ProMisE was compared with that of current risk-stratification systems (European Society of Medical Oncology [ESMO]).
  
  
  
  ProMisE decision-tree classification achieved categorization of all cases and identified 4 prognostic subgroups with distinct overall, disease-specific, and progression-free survival (P < .001). Tumors with POLE EDMs had the most favorable prognosis, and those with p53 abn the worst prognosis, and separation of the 2 middle survival curves (p53 wt and MMR-D) was observed. There were no significant differences in survival between the ESMO low-risk and intermediate-risk groups. ProMisE improved the ability to discriminate outcomes compared with ESMO risk stratification. There was substantial overlap (89%) between the p53 abn and high-risk ESMO subgroups; but, otherwise, there were no predictable associations between molecular and ESMO risk groups.
  
  
  
  Molecular classification of ECs can be achieved using clinically applicable methods and provides independent prognostic information beyond established clinicopathologic risk factors available at diagnosis. Consistent, biologically relevant categorization enables stratification for clinical trials and/or targeted therapy, identification of women who are at increased risk of having Lynch syndrome, and may guide clinical management. Cancer 2017;123:802-13. © 2016 American Cancer Society.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Aline
authors.initials: A
authors.lastname: Talhouk
authors.affiliation: Department of Human Genetics, McGill University, Research Institute of the McGill University Health Network, Montreal, Quebec, Canada.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.affiliation: Genetic Pathology Evaluation Center, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Leung
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia 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 and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Lum
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Janine
authors.initials: J
authors.lastname: Senz
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Niki
authors.initials: N
authors.lastname: Boyd
authors.affiliation: Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Judith
authors.initials: J
authors.lastname: Pike
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Anglesio
authors.affiliation: Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Janice S
authors.initials: JS
authors.lastname: Kwon
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Karnezis
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, 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 and Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics*; D004257:DNA Polymerase II / Q000235:genetics*; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation; D020125:Mutation, Missense; D009367:Neoplasm Staging; D057089:Pathology, Molecular; D000075223:Poly-ADP-Ribose Binding Proteins; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D000075223:Poly-ADP-Ribose Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004257:DNA Polymerase II; C119525:POLE protein, human
keywords: The Cancer Genome Atlas (TCGA); endometrial carcinoma; histotype; mismatch repair; p53; polymerase-ɛ (POLE); prognostic; risk-stratification system