title: Prognostic impact of fibroblast growth factor 2 in non-small cell lung cancer: coexpression with VEGFR-3 and PDGF-B predicts poor survival.
abstract: OBJECTIVE
  Fibroblast growth factor 2 (FGF2; basic fibroblast growth factor, b-FGF) and its main receptor FGFR-1 are important in both hemangiogenesis and lymphangiogenesis. Murine studies have indicated a close interplay between both FGF2 and platelet-derived growth factor-B (PDGF-B) as well as FGF2 and vascular endothelial growth factor-3 (VEGFR-3). This study investigates the prognostic impact of FGF2 and FGFR-1 in tumor cells and tumor stroma of resected non-small cell lung carcinomas (NSCLC) and explores the importance of their coexpression with VEGFR-3 or PDGF-B.
  
  
  METHODS
  Tumor tissue samples from 335 resected patients with stage I to IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers FGF2, FGFR-1, VEGFR-3, and PDGF-B.
  
  
  RESULTS
  In univariate analyses, high tumor cell FGF2 expression (p = 0.015) was a negative prognostic indicator for disease-specific survival. In tumor stroma, high FGF2 (p = 0.024) expression correlated with good prognosis. In multivariate analyses, high expression of FGF2 in tumor cells (p = 0.038) was an independent negative prognostic factor whereas increased FGF2 in stroma (p = 0.015) was a positive prognosticator. Tumor cell coexpressions of FGF2/VEGFR-3 (p < 0.001) and FGFR-1/PDGF-B (p = 0.002) were significant indicators of poor prognosis.
  
  
  CONCLUSIONS
  Expression of FGF2 in tumor cells is an independent negative prognostic factor, and the coexpressions of FGF2/VEGFR-3 and FGFR-1/PDGF-B are strongly associated with poor survival in NSCLC patients.
authors.affiliation: Institute of Clinical Medicine, University of Tromso, Norway. tom.donnem@uit.no
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes