title: Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood.
abstract: BACKGROUND
  Due to a dismal prognosis of advanced lung cancer, novel screening tools and more effective treatments are clearly needed. Lately, an increasing number of tumour-released angiogenic cytokines which affect vessel formation, tumour growth, invasion, and metastasis have been identified. Vascular endothelial growth factors (VEGFs) and basic fibroblast growth factor (bFGF) are among the most important angiogenic factors. Based on available literature, we have explored the mechanisms of angiogenesis and its prognostic significance in non-small cell lung cancer, estimated by microvessel density (MVD) and the presence of VEGF and bFGF in the tumour and blood from NSCLC patients.
  
  
  METHODS
  Several comprehensive Pubmed searches for the period January 1993 to May 2005 were performed using strategic combinations of the terms non-small cell lung cancer, angiogenesis, vascular endothelial growth factor, basic fibroblast growth factor, tumour expression, microvessel density, circulating, and serum.
  
  
  RESULTS
  NSCLC neoangiogenesis, as measured by MVD, and tumour expression of VEGF are poor prognostic factors for survival (MVD, HR 1.8-2.0; VEGF, HR 1.5). bFGF tumour expression is also associated with poor survival and more aggressive disease. When evaluating the prognostic impact of elevated VEGF levels in blood, 10 of 16 studies (63%) indicated a negative prognostic impact. Of five studies on the prognostic value of circulating bFGF, three studies reported a negative prognostic impact, while one indicated bFGF as a good prognostic factor and one was inconclusive.
  
  
  CONCLUSIONS
  Angiogenic factors are poor prognostic indicators for tumour aggressiveness and survival in NSCLC. Assessments of circulating levels of VEGF and possibly bFGF may be valuable future tools for treatment planning and monitoring of treatment effect and relapse. First, however, these blood tests need to be standardised and validated in large-scale prospective clinical trials.
authors.affiliation: Department of Oncology, University Hospital of Northern Norway, Tromsø. Roy.Bremnes@UNN.no
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
authors.forename: Rafael
authors.initials: R
authors.lastname: Sirera
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000401:mortality; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000209:etiology*; D018919:Neovascularization, Physiologic; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D013939:Thymidine Phosphorylase / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013939:Thymidine Phosphorylase; D040262:Receptors, Vascular Endothelial Growth Factor