Impact of vascular endothelial growth factor receptor 1, 2, and 3 expression on the outcome of patients with gastric cancer.

Tumor angiogenesis is a multistep interactive process in which vascular endothelial growth factor (VEGF) and its receptors have a major role. However, the clinical significance of these molecules in gastric cancer (GC) remains unclear. Our study group comprised 86 patients who underwent gastrectomy and subsequently received chemotherapy for recurrent or residual tumor. Using immunohistochemical techniques, we analyzed the expression of VEGF receptors (VEGF-R) 1, 2, and 3. VEGF-R1 expression (defined as >5% staining) was found in the tumor cells of 65 tumors (76%) and in the stromal vessels of 36 tumors (42%). VEGF-R2 expression was found in tumor cells and stromal vessels of 0 and 46 tumors (0 and 53%), respectively, and VEGF-R3 expression was found in tumor cells and stromal vessels of 0 and 75 tumors (0 and 87%), respectively. Univariate analysis revealed that VEGF-R expression correlated with shorter survival (VEGF-R1 in stromal vessels, P = 0.001; VEGF-R2 in stromal vessels, P = 0.009; VEGF-R3 in stromal vessels, P = 0.005) and lower response to S-1 (VEGF-R1 in stromal vessels, P = 0.039). Multivariate analysis of potential prognostic factors showed that VEGF-R1 and VEGF-R2 in stromal vessels were independent predictors of poor outcome. Our data suggest that VEGF-R expression can be a predictor of unfavorable clinical outcome in GC. VEGF-R are promising candidates as therapeutic targets.