title: Simultaneous EGFR and VEGF alterations in non-small cell lung carcinoma based on tissue microarrays.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) overexpression is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Furthermore, overactivation of vascular endothelial growth factor (VEGF) leads to increased angiogenesis implicated as an important factor in vascularization of those tumors.
  
  
  METHODS
  Using tissue microarray technology, forty-paraffin (n = 40) embedded, histologically confirmed primary NSCLCs were cored and re-embedded into a recipient block. Immunohistochemistry was performed for the determination of EGFR and VEGF protein levels which were evaluated by the performance of computerized image analysis. EGFR gene amplification was studied by chromogenic in situ hybridization based on the use of EGFR gene and chromosome 7 centromeric probes.
  
  
  RESULTS
  EGFR overexpression was observed in 23/40 (57.5%) cases and was correlated to the stage of the tumors (p = 0.001), whereas VEGF was overexpressed in 35/40 (87.5%) cases and was correlated to the stage of the tumors (p = 0.005) and to the smoking history of the patients (p = 0.016). Statistical significance was assessed comparing the protein levels of EGFR and VEGF (p = 0.043, k = 0.846). EGFR gene amplification was identified in 2/40 (5%) cases demonstrating no association to its overall protein levels (p = 0.241), whereas chromosome 7 aneuploidy was detected in 7/40 (17.5%) cases correlating to smoking history of the patients (p = 0.013).
  
  
  CONCLUSIONS
  A significant subset of NSCLC is characterized by EGFR and VEGF simultaneous overexpression and maybe this is the eligible target group for the application of combined anti-EGFR/VEGF targeted therapies at the basis of genetic deregulation (especially gene amplification for EGFR).
authors.affiliation: Department of Pathology, Tissue Microarrays and Computerized Image Analysis Laboratory, 417 VA Hospital (NIMTS), Athens, Greece. tsiambasecyto@yahoo.gr
authors.forename: Evangelos
authors.initials: E
authors.lastname: Tsiambas
authors.forename: Athanasios
authors.initials: A
authors.lastname: Stamatelopoulos
authors.forename: Andreas
authors.initials: A
authors.lastname: Karameris
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagiotou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Rigopoulos
authors.forename: Antonios
authors.initials: A
authors.lastname: Chatzimichalis
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris