Prognostic impact of angiogenic markers in tumor and stromal cells in non-small cell lung cancer (NSCLC)

Abstract

10596 Background: The vascular endothelial growth factors (VEGFs) -A, -C, -D and the vascular endothelial growth factor Receptors (VEGFRs) -1, -2 and -3 are important molecular markers in angiogenesis and lymphangiogenesis. This study elucidates the prognostic significance of these molecular markers in tumor cells as well as in the tumor stroma of resected NSCLC tumors. Methods: Tumor tissue samples from 335 resected patients with stage I to IIIA were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and surrounding stromal tissue from each resected specimen. Immunohistochemistry was used to evaluate the expression of each molecular marker. Results: In univariate analyses, high tumor cell expression of VEGF-A (P = .0005), VEGFR-1 (P = .013), VEGFR-2 (P = .006) and VEGFR-3 (P = .0003), were negative prognostic indicators for disease-specific survival (DSS). The most significant correlations between angiogenic marker expression and DSS were observed in patients with T2 stage and/or with sqamous cell carcinomas. In tumor stroma, however, high expression of VEGF-A (P = .017), VEGF-C (P = .003), VEGF-D (P = .009), VEGFR-1 (P = .01) and VEGFR-2 (P = .019), correlated with good prognosis. In multivariate analyses, high expression in tumor cells of VEGFR-3 (P = .007) was an independent negative prognostic factor for DSS, whereas high VEGF-C (P = .004) expression in stromal cells had an independent positive impact on survival. Conclusions: While high tumor cell expression of VEGFR-3 is an independent predictor of reduced survival in primary NSCLC, high VEGF-C expression in stromal cells is, in contrast, a favorable independent prognostic indicator. No significant financial relationships to disclose.