title: PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma.
abstract: OBJECTIVE
  To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas.
  
  
  METHODS
  We assessed PIK3CA mutational status in exon 9 and exon 20 hot spots by Sanger sequencing of DNA derived from formalin fixed paraffin embedded tissue of 57 grade 3 endometrioid, 26 serous, 11 clear cell and 5 dedifferentiated carcinomas. We correlated PIK3CA mutation status with clinicopathological and other molecular parameters. Univariate and multivariate disease specific survival analysis was performed using Kaplan-Meier and Cox regression analyses.
  
  
  RESULTS
  PIK3CA exon 9 or exon 20 missense mutations were identified in 20 of 99 (20%) high-grade endometrial carcinomas without significant difference across histological types (p=0.22). Presence of PIK3CA exon 9 or exon 20 missense mutations was associated with shorter disease specific survival within grade 3 endometrioid (p=0.0029) but not endometrial serous (p=0.57) carcinoma based on univariate analysis. Within grade 3 endometrioid carcinoma, PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p=0.0058) and showed loss of ARID1A expression (p=0.037).
  
  
  CONCLUSIONS
  PIK3CA exon 9 or exon 20 missense mutations are present across all histological types of high-grade endometrial carcinomas but a significant outcome association is only seen in grade 3 endometrioid carcinoma, suggesting a greater biological importance in this tumor type.
authors.affiliation: Department of Oncology, University of Calgary, Calgary, Alberta, Canada; Translational Laboratory, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: John B
authors.initials: JB
authors.lastname: McIntyre
authors.affiliation: University of Calgary, Calgary, Alberta, Canada; Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada. Electronic address: gsnelson@ucalgary.ca.
authors.forename: Gregg S
authors.initials: GS
authors.lastname: Nelson
authors.affiliation: University of Calgary, Calgary, Alberta, Canada; Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
authors.forename: Prafull
authors.initials: P
authors.lastname: Ghatage
authors.affiliation: Department of Oncology, University of Calgary, Calgary, Alberta, Canada; Translational Laboratory, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Don
authors.initials: D
authors.lastname: Morris
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Máire A
authors.initials: MA
authors.lastname: Duggan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Oncology, University of Calgary, Calgary, Alberta, Canada; Translational Laboratory, Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Doll
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; Calgary Laboratory Services, Calgary, Alberta, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Endometrial cancer PIK3CA missense mutation; Endometrioid carcinoma; Prognosis