title: KRAS mutation is associated with worse prognosis in stage III or high-risk stage II colon cancer patients treated with adjuvant FOLFOX.
abstract: BACKGROUND
  Although KRAS mutation has a predictive role in stage IV colorectal cancer (CRC) patients treated with anti-EGFR therapy, there have been controversies in the prognostic impact of KRAS mutation in stage II or III disease. The purpose of this study was to assess the prognostic impact of KRAS and BRAF mutation in patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX).
  
  
  METHODS
  KRAS exon 2 and BRAF codon 600 were analyzed in patients with stage II and III CRC who underwent curative resection followed by adjuvant FOLFOX. Clinicopathologic features and disease-free survival (DFS) were compared.
  
  
  RESULTS
  Among a total of 437 patients, mutational data of KRAS and BRAF were available in 388 and 433 patients, respectively. KRAS mutation (codon 12 and 13) and BRAF V600E mutation was found in 26.5 and 3.7 % of patients. DFS was significantly worse in the KRAS mutant patients compared to KRAS wild type patients (3-year DFS 79 and 92 %, p = 0.006). Multivariate analysis revealed KRAS mutation as an independent negative prognostic factor for DFS (adjusted hazard ratio 2.30, 95 % confidence interval 1.23-4.32). Among the various subtypes of KRAS mutation, G13D (3-year DFS 76 %, p = 0.008) was significantly associated with poor DFS, while G12D was not associated with prognosis (3-year DFS 86 %, p = 0.61). There was no association between BRAF mutation and DFS.
  
  
  CONCLUSIONS
  KRAS mutation has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Lee
authors.forename: Kyung Ju
authors.initials: KJ
authors.lastname: Kim
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ye Young
authors.initials: YY
authors.lastname: Rhee
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Bae
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil