Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis

Background: Vascular endothelial growth factor (VEGF) plays an important ro le in tumor growth and metastasis. We investigated the prognostic significa nce of VEGF overexpression, intratumoral microvessel density (MVD), and ang iolymphatic invasion in stage Ia-b non-small cell lung cancer (NSCLC). Methods: Eighty-five patients undergoing complete surgical resection of pat hologic stage Ia-b NSCLC were evaluated. The mean and median clinical follo w-up were 37.1 and 39.0 months (range, 30-34 months), respectively. Paraffi n-embedded tumor specimens were stained with VEGF and CD31 (a specific endo thelial marker) using immunohistochemical methods. VEGF staining was evalua ted, by combining both percentage of positive tumor cells and staining inte nsity, as low (negative and < 20% of tumor cells showing weak positivity), or high (>20% of tumor cells showing strong positivity). CD31 staining was expressed as MVD per high power field at 400x magnification. Angiolymphatic invasion was expressed as either presence or absence. Results: Low VEGF expression was seen in 25 (29%) patients, and high VEGF e xpression was seen in 60 (71%) patients. The survival rate in patients with low VEGF expression was significantly higher (80%) than that in those with high VEGF expression (48%, P = .018). The mean MVD in the low VEGF group w as 23.7 +/- 5.7 vs. 34.4 +/- 9.3 in the high VEGF group (P = .001). Patient s with high MVD also had a significantly lower survival rate than did those with low MVD count (46% vs. 73%, P = .0053). Age, sex, tumor type, and tum or differentiation were not found to be associated with overall survival. T he presence of angiolymphatic invasion and T2 stage (i.e., tumor size > 3 c m) were associated with decreased survival. High VEGF expression, tumor siz e, and angiolymphatic invasion emerged as three independent factors predict ing worsening prognosis using multivariate analysis. Conclusion: High VEGF expression within stage I NSCLC is closely associated with high intratumoral angiogenesis and poor prognosis. Immunohistochemica l evaluation of T stage and VEGF expression along with examination of angio lymphatic invasion perioperatively may aid in predicting prognosis. Adjuvan t therapies aimed at retarding tumor angiogenesis may be considered for sta ge I NSCLC patients with high VEGF levels.