OBJECTIVE To examine the expression of vascular endothelial growth factor C(VEGF-C)in human esophageal squamous cell carcinoma(ESCC), and to clarify its role in lymphatic metastasis in ESCC patients. METHODS Esophageal carcinoma EC9706 cel s and samples from 49 patients with primary ESCC were investigated by using S-P immunohisto- chemistry(IHC),the semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR)and in situ hybridization(ISH)methods for VEGF-C expression. RESULTS VEGF-C positive expression was found in EC9706 cells through IHC,ISH and RT-PCR.Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC.There was a significant difference between the expres- sion of VEGF-C in a lymph-node-positive group compared to a node-nega- tive group(χ2=4.7,P<0.05).Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC.There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group(χ2=31.3,P<0.01).The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group.Of 49 ESCC tissues,RT-PCR for VEGF-C mRNA was observed positively in 29 cases.There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group(χ2=23.3, P<0.01).The expression of VEGF-C was significantly higher in the lymph- node-positive group compared to the node-negative group.Expressions of VEGF-C were not significantly associated with age,gender,and pathological grade.There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH(χ2=18.5,P<0.01)in ESCC cases,but with no significant difference between the two methods. CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC.There was a close correlation between VEGF-C expression and lymph node metastasis.VEGF-C can serve as a useful prognostic factor for ESCC patients.