Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis

Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF protein overexpression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. The prognostic significance of VEGF overexpression in gastric cancer remains controversial. Electronic databases updated to July 2011 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 30 studies (n = 3,999 patients) that evaluated the correlation between VEGF overexpression detected by immunohistochemistry and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-A overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio] = 1.49, 95 % CI [confidence interval]: 1.22-1.77) and disease free survival (DFS) (HR = 1.85, 95 % CI: 1.38-2.32) in patients with gastric cancer. However, VEGF-C overexpression did not significantly correlate with OS (HR = 1.24, 95 % CI: 0.92-1.56) or DFS (HR = 1.15, 95 % CI: 0.78-1.52). VEGF-D is an unfavorable indicator of OS (HR = 1.68, 95 % CI: 1.02-2.34) and DFS (HR = 1.88, 95 % CI: 1.07-2.70) in patients with gastric cancer. VEGF-A and VEGF-D overexpression indicated a poor prognosis for patients with gastric cancer. VEGF-C overexpression was not associated with poor prognosis in patients with gastric cancer. The prognostic value of VEGF on survival still needs further larger prospective trials to be confirmed.