title: Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis.
abstract: OBJECTIVE
  Currently, one of the most commonly available biomarkers in the treatment of patients with colorectal liver metastases (CRLM) is the Kirsten rat sarcoma viral oncogene homolog (KRAS); however, the prognostic implications of specific mutations of the KRAS gene are still not well defined.
  
  
  OBJECTIVE
  To investigate the prognostic impact of specific KRAS mutations on patients undergoing liver resection for CRLM.
  
  
  METHODS
  This retrospective single-center study was conducted from January 1, 2003, to December 31, 2013. Data about specific KRAS mutations for 331 patients who underwent hepatic resection for CRLM at Johns Hopkins Hospital between 2003 and 2013 were analyzed. Clinicopathological characteristics, perioperative details, and outcomes were stratified by specific KRAS mutation at codons 12 and 13.
  
  
  METHODS
  Resection of CRLM.
  
  
  METHODS
  Overall survival (OS) and recurrence-free survival.
  
  
  RESULTS
  A mutated KRAS (mtKRAS) was identified in 91 patients (27.5%). At a median follow-up of 27.4 months, recurrence was observed in 48 patients (52.7%) with mtKRAS and 130 patients (54.2%) with wild-type KRAS (wtKRAS) (P = .82). Median and 5-year survival among patients with mtKRAS was 32.4 months and 32.7%, respectively, vs 58.5 months and 46.9%, respectively, for patients with wtKRAS (P = .02). Patients with KRAS codon 12 mutations had worse OS (hazard ratio [HR], 1.54; 95% CI, 1.05-2.27; P = .03) vs those with wtKRAS, whereas a KRAS codon 13 mutation was not associated with prognosis (HR, 1.47; 95% CI, 0.83-2.62; P = .19). Among the 6 most common mutations in codons 12 and 13, only G12V (HR, 1.78; 95% CI, 1.00-3.17; P = .05) and G12S (HR, 3.33; 95% CI, 1.22-9.10; P = .02) were associated with worse OS compared with patients with wtKRAS (both P < .05). Among patients who recurred, G12V (HR, 2.96; 95% CI, 1.32-6.61; P = .01), G12C (HR, 6.74; 95% CI, 2.05-22.2; P = .002), and G12S mutations (HR, 4.91; 95% CI, 1.52-15.8; P = .01) were associated with worse OS (both P < .05).
  
  
  CONCLUSIONS
  G12V and G12S mutations of codon 12 were independent prognostic factors of worse OS. Among patients who recurred after resection of CRLM, G12V, G12C, and G12S mutations were associated with worse OS. Information on specific KRAS mutations may help individualize therapeutic and surveillance strategies for patients with resected CRLM.
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Georgios Antonios
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Yuhree
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gaya
authors.initials: G
authors.lastname: Spolverato
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Aslam
authors.initials: A
authors.lastname: Ejaz
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Rohan
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Cosgrove
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Anders
authors.affiliation: Department of Surgery, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Georgios
authors.initials: G
authors.lastname: Karagkounis
authors.affiliation: Department of Surgery, University of Texas Southwestern, Dallas.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland6Deputy Editor, JAMA Surgery.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins