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AIM: To investigate the expression of vascular endothelial growth factor-c (VEGF-C) mRNA and microvessel density (MVD) in human esophageal squamous cell carcinoma (ESCC) and its relationship with clinical significance.METHODS: Specimens obtained from 43 patients undergoing surgical resection for ESCC were used in this study. The expression of VEGF-C mRNA was examined by in situ hybridization. Tumor MVD was determined immunohistochemically with anti-CD31 antibody and estimated by image analysis. Ten sections of adjacent normal mucosa were also examined.RESULTS: VEGF-C mRNA expression was detected in cytoplasm of carcinoma cells. Of the 43 ESCC patients studied, 18 cases (41.9%) were positive for VEGF-C mRNA. No VEGF-C mRNA expression was observed in normal esophageal mucosa. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P ＜ 0.05). Furthermore,histological grade (differentiation) tended to correlate with VEGF-C mRNA expression, but was not statistically significant (P ＞0.05). In tumor lesions, the MVD was significantly greater than that in normal esophageal mucosa. MVD correlated significantly with lymph node metastasis, TNM stage and depth of invasion (P＜0.05),but not with histological grade (differentiation) (P＞0.05).Lesions with VEGF-C mRNA expression had a significantly higher MVD than that of those without VEGF-C mRNA expression (P＜0.05).CONCLUJSION: VEGF-C plays a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in ESCC. VEGF-C is one of the important predictors of the biological behavior in ESCC.