title: Correlation of EGFR mutations with chromosomal alterations and expression of EGFR, ErbB3 and VEGF in tumor samples of lung adenocarcinoma patients.
abstract: BACKGROUND
  Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are frequently detected in lung adenocarcinomas with bronchioloalveolar (BAC) differentiation and have been associated with increased response to small molecule EGFR inhibitors in some clinical studies. However, further molecular characterization of tumor cells carrying EGFR mutations (EGFR-mut) is warranted.
  
  
  METHODS
  By DNA sequencing, 120 patients with lung adenocarcinomas (70 tumors with BAC components) were screened for EGFR mutations within exons 18-21. Performing comparative genomic hybridization (CGH) and immunohistochemistry, chromosomal imbalances and protein expression levels of EGFR, ErbB3 and VEGF (vascular endothelial growth factor) were analyzed, respectively.
  
  
  RESULTS
  EGFR mutations were detected in 20/120 tumors. Tumors with BAC components carried more frequently EGFR mutations compared to adenocarcinomas without BAC histology (17/70=24% vs 3/50=6.0%; p=0.012). In a subsequent matched-pair analysis, CGH-analysis demonstrated similar mean numbers of chromosomal imbalances for EGFR mutated and wild-type tumors (8.6 vs 7.8 gains; 2.4 vs 2.7 losses), respectively. Furthermore, tumors with mutated EGFR demonstrated gains in chromosomes 7p, 16p and 20q and losses in chromosome 8p. Interestingly, EGFR mutated tumors showed higher VEGF expression (p=0.03) while differences in EGFR expression were not statistically significant.
  
  
  CONCLUSIONS
  EGFR gene mutations are frequently seen in lung adenocarcinomas with BAC differentiation and can be linked to chromosomal imbalances and increased VEGF expression.
authors.affiliation: Thoraxklinik Heidelberg, University of Heidelberg, 69126 Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Reinmuth
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Elizabeth Chang
authors.initials: EC
authors.lastname: Xu
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Martin
authors.initials: M
authors.lastname: Granzow
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Hendrik
authors.initials: H
authors.lastname: Dienemann
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Felix J F
authors.initials: FJ
authors.lastname: Herth
authors.forename: Sandra
authors.initials: S
authors.lastname: Gottschling
authors.forename: Harald
authors.initials: H
authors.lastname: Lahm
authors.forename: Martin
authors.initials: M
authors.lastname: Steins
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors; D020893:Receptor, ErbB-3