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.