Prognostic Significance of the Expression of Vascular Endothelial Growth Factors A, B, C, and D and Their Receptors R1, R2, and R3 in Patients With Nonsmall Cell Lung Cancer

BACKGROUND: Lung cancer is the leading cause of cancer death in the world. The objective of this study was to investigate the expression of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) in patients with nonsmall cell lung cancer (NSCLC) and its correlation with the prognosis for patients with lung cancer. METHODS: The expression status of VEGFs and VEGFRs was examined in 48 nonconsecutive specimens of primary lung cancer by immunohistochemistry. Correlations between the expression of VEGFs and VEGFRs and clinicopathologic parameters were analyzed. RESULTS: Nineteen of 48 samples (39.6%) were moderately/highly immunoreactive for VEGF-A, 6 samples (12.5%) were reactive for VEGF-B, 14 samples (29.2%) were reactive for VEGF-C, 11 samples (22.9%) were reactive for VEGF-D, 20 samples (41.7%) were reactive for VEGFR1, 26 samples (54.2%) were reactive for VEGFR2, 20 samples (41.7%) were reactive for VEGFR3, and 19 samples (39.6%) were reactive for nuclear expression of VEGFR3. Patients with moderate/high VEGF-C, VEGFR1, and VEGFR2 expression had worse survival, whereas patients with moderate/high VEGF-D and nuclear VEGFR3 expression had better survival. After adjusting according to tumor stage, VEGF-B and VEGF-D expression had a significant correlation with worse survival in patients with stage I and 11 disease. Patients with stage III and IV disease who had VEGFR1 and VEGFR2 expression had worse survival, whereas the expression of VEGF-D was correlated significantly with better survival. Finally, stage, VEGF-D expression, and VEGFR1 expression were significantly independent prognostic predictors. CONCLUSIONS: The results of the current study indicated that the over-expression of VEGFs and VEGFRs plays an important role in the survival of patients with NSCLC. The inclusion of angiogenic factors in the standard pathologic study of lung cancer may improve the clinical evaluation of patients with NSCLC. Cancer 2009;115:1701-12. (C) 2009 American Cancer Society.