title: Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery.
abstract: BACKGROUND
  Conventional treatment for locally advanced rectal cancer usually combines neoadjuvant radiochemotherapy and surgery. Until recently, there have been limited predictive factors (clinical or biological) for rectal tumor response to conventional treatment. KRAS, BRAF and PIK3CA mutations are commonly found in colon cancers. In this study, we aimed to determine the mutation frequencies of KRAS, BRAF and PIK3CA and to establish whether such mutations may be used as prognostic and/or predictive factors in rectal cancer patients.
  
  
  METHODS
  We retrospectively reviewed the clinical and biological data of 98 consecutive operated patients between May 2006 and September 2009. We focused in patients who received surgery in our center after radiochemotherapy and in which tumor samples were available.
  
  
  RESULTS
  In the 98 patients with a rectal cancer, the median follow-up time was 28.3 months (4-74). Eight out of ninety-eight patients experienced a local recurrence (8%) and 17/98 developed distant metastasis (17%). KRAS, BRAF and PIK3CA were identified respectively in 23 (23.5%), 2 (2%) and 4 (4%) patients. As described in previous studies, mutations in KRAS and BRAF were mutually exclusive. No patient with local recurrence exhibited KRAS or PIK3CA mutation and one harbored BRAF mutation (12.5%). Of the seventeen patients with distant metastasis (17%), 5 were presenting KRAS mutation (29%), one BRAF (5%) and one PIK3CA mutation (5%). No relationship was seen between PIK3CA, KRAS or BRAF mutation and local or distant recurrences.
  
  
  CONCLUSIONS
  The frequencies of KRAS, BRAF and PIK3CA mutations in our study were lower than the average frequencies reported in colorectal cancers and no significant correlation was found between local/distant recurrences and KRAS, BRAF or PIK3CA mutations. Future studies with greater number of patients, longer follow-up time and greater power to predict associations are necessary to fully understand this relationship.
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, Lyon 69008, France. olfa.derbel@lyon.unicancer.fr
authors.forename: Olfa
authors.initials: O
authors.lastname: Derbel
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Françoise
authors.initials: F
authors.lastname: Desseigne
authors.forename: Michel
authors.initials: M
authors.lastname: Rivoire
authors.forename: Pierre
authors.initials: P
authors.lastname: Meeus
authors.forename: Patrice
authors.initials: P
authors.lastname: Peyrat
authors.forename: Mattia
authors.initials: M
authors.lastname: Stella
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martel-Lafay
authors.forename: Anne-Isabelle
authors.initials: AI
authors.lastname: Lemaistre
authors.forename: Christelle
authors.initials: C
authors.lastname: de La Fouchardière
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins