Serum VEGF-A and Tumor Vessel VEGFR-2 Levels Predict Survival in Caucasian but Not Asian Patients Undergoing Resection for Gastric Adenocarcinoma

Background: Clinical trials of agents targeting the vascular endothelial growth factor A (VEGF-A) pathway in gastric adenocarcinoma (GA) suggest that these therapies may have varying efficacy in different races. Methods: VEGF-A in serum and/or VEGF receptor 2 (VEGFR-2) in CD31-positive tumor vessels (VEGFR-2/CD31) were measured in 118 Caucasians and 263 Asians who underwent gastric resection at two institutions and correlated with overall survival (OS). Blood was drawn before any treatment. Patients receiving neoadjuvant treatment were excluded from VEGFR-2 analysis. Results: Compared with Asians, Caucasians were older (mean age 66–73 vs 59–62 years), had more proximal tumors, and had more advanced TNM stage. In the VEGF-A cohort, Caucasians had a median VEGF-A level that was 95 % higher than that of Asians and a much higher standard deviation (88 ± 6.206 vs 45 ± 76 pg/ml, p < 0.001). The 5-year OS for patients with low versus high VEGF-A levels was 72 versus 43 % in Caucasians (p = 0.001) and 86 versus 77 % in Asians (p = 0.236). In the VEGFR-2 cohort, OS was worse in Caucasians with high VEGFR-2/CD31 levels (49 vs 73 %, p = 0.038), while there was no significant difference in OS in Asians (80 vs 90 %, p = 0.119). On multivariate analyses of significant prognostic factors (excluding treatment factors and margin status), serum VEGF-A and tumor VEGFR-2/CD31 levels were independent predictors of OS only in Caucasians. Conclusions: In patients with resectable GA, VEGF-A and VEGFR-2/CD31 levels are independent predictors of OS in Caucasians but not in Asians, suggesting varying importance of this pathway in GA progression among different races.