Immunohistochemical study of vascular endothelial growth factor‑C/vascular endothelial growth factor receptor‑3 expression in oral tongue squamous cell carcinoma: Correlation with the induction of lymphangiogenesis

Naruse,Tomofumi; Yanamoto,Souichi; Yamada,Shin‑Ichi; Takahashi,Hidenori; Matsushita,Yuki; Imayama,Naomi; Ikeda,Hisazumi; Shiraishi,Takeshi; Fujita,Shuichi; Ikeda,Tohru; Asahina,Izumi; Umeda,Masahiro

doi:10.3892/ol.2015.3565

Immunohistochemical study of vascular endothelial growth factor‑C/vascular endothelial growth factor receptor‑3 expression in oral tongue squamous cell carcinoma: Correlation with the induction of lymphangiogenesis

Authors:
- Tomofumi Naruse
- Souichi Yanamoto
- Shin‑Ichi Yamada
- Hidenori Takahashi
- Yuki Matsushita
- Naomi Imayama
- Hisazumi Ikeda
- Takeshi Shiraishi
- Shuichi Fujita
- Tohru Ikeda
- Izumi Asahina
- Masahiro Umeda
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Affiliations: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852‑8588, Japan, Department of Regenerative Oral Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852‑8588, Japan, Department of Oral Pathology and Bone Metabolism, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852‑8588, Japan
Published online on: August 4, 2015 https://doi.org/10.3892/ol.2015.3565
Pages: 2027-2034
Copyright: © Naruse et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to elucidate the associations between the expression of the vascular endothelial growth factor‑C (VEGF‑C)/VEGF receptor‑3 (VEGFR‑3) axis and lymphangiogenesis, regional lymph node metastasis and clinicopathological factors in oral tongue squamous cell carcinoma (OTSCC) using immunohistochemistry. The expression of VEGF‑C, VEGFR‑3 and podoplanin was immunohistochemically evaluated in specimens obtained from 65 patients with OTSCC (T1‑2, N0) who had undergone radical surgery alone. The associations between the expression of VEGF‑C, VEGFR‑3 and podoplanin, and lymphangiogenesis, regional lymph node metastasis and clinocopathological factors were determined by immunohistochemical analysis. VEGF‑C, VEGFR‑3 and combined VEGF‑C/VEGFR‑3 expression was significantly higher in cases with regional recurrence compared with those without lymph node involvement (P<0.001). As regards lymphangiogenesis, a significant correlation was observed between podoplanin expression and VEGF‑C, VEGFR‑3 and combined VEGF‑C/VEGFR‑3 expression (P<0.001). therefore, lymphangiogenesis in the peritumoral stroma was associated with lymph node metastasis. However, podoplanin expression did not exhibit a significant correlation with the progression of lymph node metastasis. The results of the present study suggest that the VEGF‑C/VEGFR‑3 axis may be associated with lymph node metastasis through lymphangiogenesis. Determining the VEGF‑C/VEGFR‑3 expression status may help predict which patients will develop regional recurrence and provide novel targets for therapies to suppress lymph node metastasis in the treatment of OTSCC.

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