Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma : Association with angiogenesis and tumor progression

Angiogenesis is essential for solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator in vivo. Conversely, there have been few studies of the association between angiogenic factor expression and angiogenesis in esophageal carcinoma. The authors examined VEGF expression and microvessel density in esophageal squamous cell carcinomas to clarify the association of VEGF expression with the clinicopathologic features of the disease. Surgical specimens from 75 primary esophageal squamous cell carcinomas were examined for VEGF expression and microvessel density by immunocytochemical staining. Original anti-VEGF polyclonal antibody was used to determine VEGF expression, and antifactor VIII antibody was used to determine microvessel density. The isoforms of VEGF mRNA were determined by reverse transcriptase-polymerase chain reaction. Thirty-five (46.7%) of the 75 esophageal carcinomas were positive for VEGF protein. There was a close correlation between microvessel density and VEGF positivity (P = 0.0002). High VEGF levels were significantly associated with well differentiated tumors, advanced stage (depth of invasion and blood vessel invasion), high incidence of distant metastases after surgery, and poorer prognosis. The results of this study suggest that VEGF expression is associated with tumor progression and poor prognosis by stimulating angiogenesis in esophageal squamous cell carcinoma.