title: PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy.
abstract: OBJECTIVE
  Mutational activation of PIK3CA is associated with poor prognosis in patients with solid tumors, and may predict favorable response to PI3K/AKT/mTOR pathway inhibitors. However, PIK3CA mutational status has not previously been evaluated in patients with cervical carcinoma treated with radical chemoradiotherapy (CRT). The aims of this study were (1) to evaluate the frequency of PIK3CA mutations in patients with cervical cancer treated with radical CRT and (2) to examine the effect of tumor PIK3CA mutational status in pre-treatment biopsies on overall survival (OS) and progression-free survival (PFS).
  
  
  METHODS
  Patients with cervical cancer, treated at a single institution with radical CRT, from 1999 to 2008, were eligible for this retrospective study. Pre-treatment tumor biopsies (n=157) were retrieved. Genomic DNA was extracted from tumor blocks, and exons 9 and 20 of the PIK3CA gene were sequenced for mutations.
  
  
  RESULTS
  Eighty-two tumors were sequenced for both exon 9 and exon 20. 19/82 (23%) tumors were PIK3CA mutation positive; of these 84% were squamous cell carcinomas. 79% of mutations were in exon 9. PIK3CA mutation status was strongly associated with overall survival (OS) in FIGO stage IB/II patients, unadjusted HR 6.0 (95% CI 2.1-17.5), p=0.0002, but not stage III/IVA patients, unadjusted HR 1.0 (95% CI 0.32-3.1), p=0.98.
  
  
  CONCLUSIONS
  In cervical cancer patients treated with CRT, tumor PIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers. Further evaluation with a larger dataset will be required to validate these findings to inform potential clinical trials designs involving PI3K/AKT/mTOR pathway inhibitors.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary AB, Canada.
authors.forename: John B
authors.initials: JB
authors.lastname: McIntyre
authors.forename: Jackson S
authors.initials: JS
authors.lastname: Wu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Craighead
authors.forename: Tien
authors.initials: T
authors.lastname: Phan
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Susan P
authors.initials: SP
authors.lastname: Lees-Miller
authors.forename: Prafull
authors.initials: P
authors.lastname: Ghatage
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
authors.forename: Corinne M
authors.initials: CM
authors.lastname: Doll
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D059248:Chemoradiotherapy; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human