title: Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases.
abstract: BACKGROUND
  Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012.
  
  
  RESULTS
  mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS: 43 months; TTR: 19 months) compared with mEGFR (OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS: KRAS G12V: 26 months vs
  
  
  METHODS
  60 months; DFS: KRAS G12V: 15 months vs
  
  
  METHODS
  24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28-0.65), P<0.0001 for OS; HR: 0.67 (0.48-0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR: 0.01, (0.001-0.08), P<0.0001).
  
  
  CONCLUSIONS
  mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Nouvel Hôpital Civil, 67000 Strasbourg, France.|Reasearch Unit EA3430: Tumoral Progression and Micro-environment, Translational and Epidemiological Approaches, Translational Medicine Federation, Strasbourg University. 67000 Strasbourg, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Renaud
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Nouvel Hôpital Civil, 67000 Strasbourg, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Falcoz
authors.affiliation: Department of Biostatistics, Strasbourg University Hospital. 67000 Strasbourg, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Schaëffer
authors.affiliation: Reasearch Unit EA3430: Tumoral Progression and Micro-environment, Translational and Epidemiological Approaches, Translational Medicine Federation, Strasbourg University. 67000 Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guenot
authors.affiliation: Reasearch Unit EA3430: Tumoral Progression and Micro-environment, Translational and Epidemiological Approaches, Translational Medicine Federation, Strasbourg University. 67000 Strasbourg, France.|Department of General and Digestive Surgery, Strasbourg University Hospital, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Romain
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Nouvel Hôpital Civil, 67000 Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Olland
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Nouvel Hôpital Civil, 67000 Strasbourg, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Reeb
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Nouvel Hôpital Civil, 67000 Strasbourg, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santelmo
authors.affiliation: Department of Pathology, Strasbourg University Hospital. 67000 Strasbourg, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.affiliation: Department of Molecular Biology, Oncobiology Laboratory, Regional Institute of Cancer Strasbourg University Hospital, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Legrain
authors.affiliation: Department of Molecular Biology, Oncobiology Laboratory, Regional Institute of Cancer Strasbourg University Hospital, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Voegeli
authors.affiliation: Reasearch Unit EA3430: Tumoral Progression and Micro-environment, Translational and Epidemiological Approaches, Translational Medicine Federation, Strasbourg University. 67000 Strasbourg, France.|Department of Molecular Biology, Oncobiology Laboratory, Regional Institute of Cancer Strasbourg University Hospital, Hôpital de Hautepierre, Strasbourg, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Beau-Faller
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Nouvel Hôpital Civil, 67000 Strasbourg, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Massard
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins