title: Epidermal growth factor receptor and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue-specific amino acid substitutions are associated with different histopathological prognostic factors in resected non-small-cell lung cancer.
abstract: Epidermal growth factor receptor (mEGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue (mKRAS) mutations are the two main oncogenic drivers in resected non-small-cell lung cancer (NSCLC). We aimed to evaluate the correlation between histopathological prognostic factors and these mutations in resected NSCLC.
  
  
  
  We retrospectively reviewed data from 841 patients who underwent a surgical resection with a curative intent for NSCLC between 2007 and 2012.
  
  
  
  KRAS mutations were observed in 255 patients (32%) and mEGFR in 103 patients (12%). A correlation was observed between mKRAS patients and lymph node involvement [Cramer's V: 0.451, P < 0.001, OR: 7.5 (95% CI: 5.3-10.7), P < 0.001]. Otherwise, a correlation was observed between mKRAS and the risk of harbouring 2 N2 stations [Cramer's V: 0.235, P = 0.02, OR: 3.04 (95% CI: 1.5-6.3), P = 0.004]. High lymph node ratio and angioinvasion were also significantly more frequent in mKRAS [Cramer's V: 0.373, P < 0.001, OR: 6.37 (95% CI: 3.9-10.5), P < 0.001; and Cramer's V: 0.269, P < 0.001, OR: 3.25 (95% CI: 2.4-4.4), P < 0.001, respectively]. Skip N2 and microscopic N2 were significantly more frequent in mEGFR [Cramer's V: 0.459, P < 0.001, OR: 18 (95% CI: 5.6-57.8), P < 0.001; and (Cramer's V: 0.45, P < 0.001 OR: 21.14 (95% CI: 9.2-48.3), P < 0.001, respectively].
  
  
  
  We observed a correlation between mKRAS and negative histopathological prognostic factors and between mEGFR and positive prognostic factors. One can wonder whether histopathological prognostic factors are only clinical reflections of molecular alterations.
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, Strasbourg University Hospital, Strasbourg, France sterenaud0@gmail.com.|Research Unit EA 3430: Tumoral Progression and Micro-Environment, Translational and Epidemiological Approaches, Translational Medicine Federation, Strasbourg University, Strasbourg, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Renaud
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 Biostatistics, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Schaeffer
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Olland
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Reeb
authors.affiliation: Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santelmo
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: Department of Pathology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Weingertner
authors.affiliation: Department of Pathology, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.affiliation: Research Unit EA 3430: Tumoral Progression and Micro-Environment, Translational and Epidemiological Approaches, Translational Medicine Federation, Strasbourg University, 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, Strasbourg, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Massard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; 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*; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Epidermal growth factor receptor; Histopathological; Non-small-cell lung cancer; Surgery; v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue