Abstract
Lymph node metastasis is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor (VEGF)-C and its receptor, VEGF receptor-3 (VEGFR-3), are key in the process of lymphangiogenesis. The present study immunohistochemically examined the expression of VEGF-C, VEGFR-3 and D2-40 in 119 patients with ESCC, and microlymphatic vessel density (MLVD) was calculated based on D2-40 expression counts. Positive expression of VEGF-C was found to correlate significantly with depth of tumor invasion, lymphatic invasion and lymph node metastasis (P<0.001, P<0.0001 and P<0.0001, respectively). Patients with deeper tumor invasion showed higher positivity of VEGFR-3 expression (P<0.05), while patients with lymph node metastasis showed higher MLVD (P<0.05). When patients were divided into three groups according to the expression of VEGF-C and VEGFR-3, patients with coexpression of VEGF-C and VEGFR-3 exhibited poorer prognosis and higher MLVD. The VEGF-C/VEGFR-3 axis is important in tumor lymphangiogenesis.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of gastrointestinal cancer, due to the relatively high risk of metastasis even in the early stage
The incidence of lymph node metastasis tended to occur in patients with positive expression of VEGF receptor‐3 (VEGFR‐3); the correlation was not significant
Lymphangiogenesis represents an important step in tumor progression and metastasis
Summary
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of gastrointestinal cancer, due to the relatively high risk of metastasis even in the early stage. Two members of the vascular endothelial growth factor (VEGF) family, VEGF‐C and VEGF‐D, reportedly induce angiogenesis, and lymphangiogenesis via VEGF receptor (VEGFR)‐2 and VEGFR‐3 on lymphatic endothelial cells [3,4]. These receptors regulate lymphangiogenesis, and enhance lymphatic metastasis [5]. VEGF‐C and VEGFR‐3, which together have been proposed as a marker for lymphatic endothelial cells, have recently been reported to be expressed by tumor cells in correlation with the invasion, metastasis and progression of cancer cells [6,7,8]
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