title: 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.
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.
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Imayama
authors.affiliation: Department of Regenerative Oral Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Hisazumi
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Regenerative Oral Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiraishi
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Regenerative Oral Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Asahina
authors.affiliation: Department of Clinical Oral Oncology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki 852-8588, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
keywords: podoplanin; regional recurrence; tongue cancer; vascular endothelial growth factor receptor-3; vascular endothelial growth factor-C