title: Consistent mutation status within histologically heterogeneous lung cancer lesions.
abstract: OBJECTIVE
  Activating epidermal growth factor receptor (EGFR) and KRAS mutations characterize molecular subgroups of non-small-cell lung cancer (NSCLC) with a strong predictive value for response to EGFR inhibitor therapy. However, the temporal occurrence and clonal stability of these mutations during the course of cancer progression are debated. The aim of this study was to characterize the presence of EGFR and KRAS mutations in histologically different areas of primary NSCLC lesions.
  
  
  RESULTS
  Formalin-fixed paraffin-embedded cancer specimens from six cases with EGFR mutations and five cases with KRAS mutations were selected from a pool of primary resected NSCLC patients. From each tumour, three morphologically distinct areas were manually microdissected and analysed for the presence of mutations. The results demonstrated consistent EGFR and KRAS mutation status in the different histological areas of all primary tumours.
  
  
  CONCLUSIONS
  The results support the concept that activating EGFR and KRAS mutations are oncogenic events that are consistently present throughout the primary tumour independently of histological heterogeneity. Thus, for molecular diagnostics, any part of the tumour is likely to be representative for EGFR and KRAS mutation testing.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johanna Sofia Margareta
authors.initials: JS
authors.lastname: Mattsson
authors.forename: Juliana
authors.initials: J
authors.lastname: Imgenberg-Kreuz
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D042282:Microdissection; D009154:Mutation; 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)