title: Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy.
abstract: OBJECTIVE
  To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations.
  
  
  RESULTS
  Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype.
  
  
  CONCLUSIONS
  POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Salwa
authors.initials: S
authors.lastname: Bakhsh
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Kinloch
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lien N
authors.initials: LN
authors.lastname: Hoang
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.affiliation: Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital and University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D004257:DNA Polymerase II / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D000075223:Poly-ADP-Ribose Binding Proteins; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D000075223:Poly-ADP-Ribose Binding Proteins; D004257:DNA Polymerase II; C119525:POLE protein, human
keywords: POLE; TCGA; endometrial carcinoma; mutations