Vascular endothelial growth factor expression and neovascularization in Barrett's carcinoma

Angiogenesis is essential for tumor growth and metastasis. An association between microvessel density, a measure of tumor angiogenesis, and conventional prognostic variables has been shown for many tumor entities. For Barrett's carcinoma, the results are controversial. Immature vessels formed in tumors are structurally and functionally different from those in mature vessels. The relation between mature and immature vessels as a prognostic factor for Barrett's carcinoma has not been assessed. Specimens from 45 R0-resected Barrett's carcinomas were immunostained for vascular endothelial growth factor (VEGF), CD 31, and smooth muscle a-actin to discriminate between mature and immature vessels. VEGF staining was evaluated quantitatively by measuring optical density with a new computer-based program and expressed as a percentage of the staining (juvenile placental tissue) on control slides. The neovascularization coefficient (i.e., the relation between mature and immature vessels) was estimated with an interactive analytic computer program. The median survival of the study group was 45.7 months. The neovascularization coefficient correlated with the histopathologic classification (p<0.001). Survival time in patients with a low neovascularization coefficient was significantly better than the survival time in patients with a high neovascularization coefficient (p=0.021). VEGF expression did not correlate with clinicopathologic data (p>0.05) or with patient survival (p>0.05). The tumors with a high neovascularization coefficient did not have significantly elevated VEGF expression. Based on a strong quantitative computer evaluation program, the present study indicates that neovascularization has an important impact on the survival of patients with Barrett's carcinoma. However, VEGF does not appear to be the vascular growth factor stimulating neovascularization in Barrett's carcinoma patients.