Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer

Abstract

BackgroundPlatelet-derived growth factors (PDGFs) and vascular endothelial growth factors and their receptors [platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs)] are related to both angiogenesis and lymphangiogenesis and are important targets in new cancer treatment strategies. We aimed to study the PDGFs/PDGFRs and correlations with lymph node metastasis (LNM) and investigate the prognostic impact of the co-expression of PDGF-B and VEGFR-3 and its correlation with LNM. Patients and methodsTumor tissue samples from 335 resected patients with stage I–IIIA non-small-cell lung cancer (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 PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFR-α, PDGFR-β, VEGFR-3 and D2-40. ResultsThere were 232 N0 and 103 N+ patients (76 N1 and 27 N2). In multivariate analyses, high tumor cell PDGF-A expression (P=0.017) correlated with LNM. Tumor cell co-expression of VEGFR-3 and PDGF-B correlated with nodal metastasis and was an independent indicator of poor prognosis (hazard ratio 4.8, confidence interval 95% 2.80–8.31, P<0.001). ConclusionTumor cell PDGF-A expression correlates with LNM, and the co-expression of PDGF-B and VEGFR-3 is strongly associated with poor survival in NSCLC patients.