Measurement of circulating levels of VEGF-A,-C,and -D and their receptors,VEGFR-1 and -2 in gastric adenocarcinoma

AIM: To analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF) -A,-C,and -D,and their receptors,VEGFR-1 and -2 in gastric adenocarcinomas. METHODS: The serum levels of VEGF family members were measured in 76 control subjects and 76 patients with gastric adenocarcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements were correlated with clinco-pathological features and survival rates. RESULTS: The serum levels of VEGF-A and its receptor,VEGFR-1,were signifi cantly higher in patients with gastric cancer than in healthy donors (t = 2.3,P = 0.02 and t = 4.2,P < 0.0001,respectively). In contrast,the serum levels of VEGF-D were signif icantly higher in control subjects than in patients (t = 2.9,P = 0.004). There was no significant difference in serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-C was associated with advanced tumor stage and presence of metastasis. VEGFR-1 was associated with metastasis,advanced overall stage,tumor differentiation and survival. VEGFR-2 levels were associated with poor tumor differentiation. There was no significant prognostic value for any of the VEGF family members or their receptors except for VEGFR-1 where high levels were associated with a poor overall survival. CONCLUSION: Serum VEGF levels vary significantly in the same cohort of patients with variable clinico-pathological features and prognostic values. The simultaneous measurement of VEGF receptors levels in sera may overcome the limitations of a single biomarker assay.