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Expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 in esophageal squamous cell carcinoma. 2014

Itaru Omoto, and Masataka Matsumoto, and Hiroshi Okumura, and Yasuto Uchikado, and Tetsuro Setoyama, and Yoshiaki Kita, and Tetsuhiro Owaki, and Yuko Kijima, and Hiroyuki Shinchi, and Sumiya Ishigami, and Shinichi Ueno, and Shoji Natsugoe
Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medicine, Kagoshima University, Kagoshima 890-8520, Japan.

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.

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