Prognostic Impact of Fibroblast Growth Factor 2 in NSCLC : Co-Expression with VEGFR-3 and PDGF-B Predicts Poor Survival

Abstract

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 co-expression with VEGFR-3 or PDGF-B. <br>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. <br>Results: In univariate analyses, high tumor cell FGF2 expression (P = 0.015) was a negative prognostic indicator for disease-specific survival (DSS). 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 GFR-1/PDGF-B (P = 0.002) were significant indicators of poor prognosis. <br>Conclusions: Expression of FGF2 in tumor cells is an independent negative prognostic factor, and the co-expressions of FGF2/VEGFR-3 and FGFR-1/PDGF-B are strongly associated with poor survival in NSCLC patients.