Role of Vascular Endothelial Growth Factor in the Progression and Prognosis of Gastric Carcinomas

Abstract

BACKGROUND: Solid tumors require neovasculization for growth and metastasis. Recently, several angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is thought to be one such angiogenic factor and is also thought to be a selective mitogen for endothelial cells. In this study, we examined the expression of VEGF and its relationship with microvessel density, and we also determined its prognostic significance in gastric cancer patients. METHODS: One hundred one specimens resected from patients with gastric carcinomas were investigated by staining with a polyclonal antibody against VEGF. Correlations between the expression of VEGF, the microvessel density, various clinicopathologic factors, and the patient's survival were studied. RESULTS: The normal gastric mucosa was not immunoreactive with an anti-VEGF antibody. VEGF was mainly localized to the cytoplasm or the membrane of the carcinoma cell. Of the 101 tumors, strong VEGF expression was detected in 48 (47.5%) tumors. VEGF expression was correlated with depth of tumor invasion, lymph-node metastasis, and stage. Microvessel density, determined by immunohistochemical staining for CD31, was significantly higher in VEGF-strong tumors than in VEGF-weak tumors. Also, patients with VEGF-strong tumors had a significantly poorer prognosis than those with VEGF-weak tumors. However, multivariate analysis indicated that the expression of VEGF was not an independent prognostic factor in patients with gastric cancer. CONCLUSIONS: The fact that VEGF expression in gastric carcinomas was more prevalent in more advanced tumors means that VEGF may contribute to the progression of the tumor. Further study is needed to evaluate the significance of VEGF as a prognostic factor.