title: KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer.
abstract: BACKGROUND
  The utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC).
  
  
  RESULTS
  KRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61-82.56) vs 56 months (95% CI: 68.71-127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93-59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17-0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14-1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations.
  
  
  METHODS
  We retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations.
  
  
  CONCLUSIONS
  KRAS exon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.|Department of Thoracic Surgery, Nancy University Hospital, Nancy, France.|Research Unit EA3430, Tumoral Progression and Micro-Environment, Epidemiological and Translational Approaches, Strasbourg University, Strasbourg, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Renaud
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.|Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerrera
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Seitlinger
authors.affiliation: Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Costardi
authors.affiliation: Department of Biostatistics, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Schaeffer
authors.affiliation: Research Unit EA3430, Tumoral Progression and Micro-Environment, Epidemiological and Translational Approaches, Strasbourg University, Strasbourg, France.|Department of General and Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Romain
authors.affiliation: Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mossetti
authors.affiliation: Department of Molecular Biology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Claire-Voegeli
authors.affiliation: Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Filosso
authors.affiliation: Department of Molecular Biology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Legrain
authors.affiliation: Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Falcoz
authors.affiliation: Department of Thoracic Surgery, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Oliaro
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Massard
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D015179:Colorectal Neoplasms / Q000235:genetics / Q000601:surgery*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D019616:Thoracic Surgical Procedures; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; codon; colorectal cancer; lung metastasectomy; surgery