title: Vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 expression in non-small cell lung cancer patients: relation to prognosis.
abstract: BACKGROUND
  The majority of patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced inoperable disease. While treatment with conventional chemotherapy has improved during the last decade the 5 years survival is still modest. Novel drugs, which selectively target aberrant elements in neoplastic cells and their microenvironment have recently been and are continuously developed including drugs inhibiting the angiogenic system. Angiogenic factor vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) seem to play key roles in tumour-induced angiogenesis. Previous studies have been inconclusive on the topic of a role for VEGF and its receptor as prognostic factors in NSCLC.
  
  
  METHODS
  Paraffin-embedded histological material from 102 patients operated for NSCLC was included and a representative block with lung cancer tissue was selected from each patient for immunohistochemical studies. The sections were incubated with primary monoclonal antibodies to VEGF-A and VEGFR2. The expression of the immunohistochemical staining was assessed semi-quantitatively by estimating the percentage and the intensity of tumour cells stained on whole tumour slides. Kaplan-Meier survival curves were generated to evaluate the significance of immunohistochemical VEGF-A and VEGFR2 expression for the prognosis.
  
  
  RESULTS
  VEGF-A and VEGFR2 expression was observed in the majority of NSCLC patients. VEGF-A expression showed a correlation to histological type with increased expression in adenocarcinomas as compared to squamous cell carcinomas. There was no statistically significant correlation between VEGF-A and VEGFR2 expression and age, gender or stage at diagnosis. Finally there was no relation between expression of VEGF-A and VEGFR2, nor an effect of high expression of both VEGF-A and VEGFR2 on survival.
  
  
  CONCLUSIONS
  In conclusion VEGF-A and VEGFR2 are expressed in NSCLC, but the immunohistochemical expression of VEGF-A and VEGFR2 has no prognostic impact in NSCLC. We show that the histological subgroups of NSCLC express VEGF-A differently, with adenocarcinomas having the highest amount. Whether these markers might be useful as clinically reliable predictive markers remains to be solved.
authors.affiliation: Department of Pathology, Herlev University Hospital, Division Gentofte, Niels Andersens vej 65, 2900 Copenhagen (Hellerup), Denmark.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bonnesen
authors.forename: Helle
authors.initials: H
authors.lastname: Pappot
authors.forename: Julie
authors.initials: J
authors.lastname: Holmstav
authors.forename: Birgit Guldhammer
authors.initials: BG
authors.lastname: Skov