Combination of Low Vascular Endothelial Growth Factor A (VEGF-A)/VEGF Receptor 2 Expression and High Lymphocyte Infiltration Is a Strong and Independent Favorable Prognostic Factor in Patients With Nonsmall Cell Lung Cancer

BACKGROUND: There seems to be a close interplay between angiogenesis and the immune system. The authors of this report investigated the prognostic role of angiogenic markers in coexpression with immune system markers in patients with nonsmall cell lung cancer (NSCLC). METHODS: Tumor resection samples from 335 patients with stage I to IIIA NSCLC were obtained, and tissue microarrays were constructed. Immunohistochemistry was used to evaluate the expression of vascular endothelial growth factor (VEGF) A (VEGF-A), VEGF receptor 2 (VEGFR-2), and lymphocytes that were positive for the cluster of differentiation 4 (CD4) and CD8 coreceptors. RESULTS: In univariate analysis, 5-year survival rates were 87% for the combination of low tumor cell expression of VEGF-A and VEGFR-2 (down arrow VEGF-A/down arrow VEGFR-2) and high tumor cell expression of CD4 and CD8 (up arrow CD4/up arrow CD8) (n = 19), 58% for mixed combinations (n = 290), and 27% for the up arrow VEGF-A/up arrow VEGFR-2 and down arrow CD4/down arrow CD8 combination (n = 26). In multivariate analysis, the coexpression of up arrow VEGF-A/up arrow VEGFR-2 and down arrow CD4/down arrow CD8 was an independent negative prognostic factor (hazard ratio, 9.16; 95% confidence interval, 2.11-39.8; P = .003). CONCLUSIONS: Low tumor cell VEGF-A and VEGFR-2 expression in combination with high adaptive immune cell expression in the tumor-related stroma had a strong and independent favorable prognostic impact in patients with NSCLC. Cancer 2010;116:4318-25. (C) 2010 American Cancer Society.