Prognostic impact of fibroblast growth factor 2 in non-small cell lung cancer: coexpression with VEGFR-3 and PDGF-B predicts poor survival

J Thorac Oncol. 2009 May;4(5):578-85. doi: 10.1097/JTO.0b013e31819f2e38.


Purpose: 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.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Adenocarcinoma, Bronchiolo-Alveolar / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / secondary
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary
  • Female
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-sis / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Retrospective Studies
  • Stromal Cells / metabolism
  • Survival Rate
  • Tissue Array Analysis
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism*


  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-sis
  • Fibroblast Growth Factor 2
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Vascular Endothelial Growth Factor Receptor-3