title: Prognostic impact of angiogenic markers in non-small-cell lung cancer is related to tumor size.
abstract: BACKGROUND
  It is thought that different families of angiogenic factors stimulate angiogenesis at different stages of tumor development. Our aim was to study whether the prognostic impact of vascular endothelial growth factors (VEGFs) and receptors (VEGFRs), platelet-derived growth factors (PDGFs) and receptors (PDGFRs) and fibroblast growth factor-2 (FGF-2) were associated with tumor size in non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Tumor tissue samples were obtained from 335 patients who had undergone resection for stage I-IIIA NSCLC, and tissue microarrays (TMAs) were constructed. Immunohistochemical techniques were used to evaluate the expression of VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, PDGF-A, PDGF-B, PDGFR-α, PDGFR-β, and FGF-2. Tumor size was categorized using the same cutoffs as in the 7th TNM classification for lung cancer.
  
  
  RESULTS
  In multivariate analysis, high VEGFR-2 (HR, 1.87, [95% CI, 1.02-3.45]; P = .043), VEGFR-3 (HR, 2.18 [95% CI, 1.28-3.71]; P = .004) and the combination of high VEGF-A and high VEGFR-2 expression (low/low vs. high/high; HR, 3.28 [95% CI, 1.47-7.31]; P = .004) were independent negative prognostic factors in T2a tumors. High PDGF-B expression (HR, 11.72 [95% CI, 3.07-44.76]; P < .001) was an independent prognostic factor in T2b tumors.
  
  
  CONCLUSIONS
  The prognostic impact of angiogenic factors depend in part on tumor size. VEGF-A/VEGFR-2 and VEGFR-3 seem to have their main impact in T2a tumors, while PDGF-B is a strong and independent prognostic factor in T2b tumors.
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso. tom.donnem@uit.no
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012189:Retrospective Studies; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D020574:Proto-Oncogene Proteins c-sis; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017479:Receptors, Platelet-Derived Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3