title: Lymphatic Vessel Density and Vascular Endothelial Growth Factor Expression in Squamous Cell Carcinomas of Lip and Oral Cavity: A Clinicopathological Analysis with Immunohistochemistry Using Antibodies to D2-40, VEGF-C and VEGF-D.
abstract: BACKGROUND
  Squamous cell carcinoma (SCC) of the oral region often metastasizes to the cervical lymph nodes. To investigate whether the risk of cervical lymph node metastasis are predictable through lymphatic vessel density (LVD) and vascular endothelial growth factor (VEGF) expression, we assessed the relationship between LVD and clinicopathological parameters, and VEGF expression in SCC of the oral region.
  
  
  METHODS
  The subjects were 109 patients with SCC of the oral region including the lip. Clinicopathological parameters examined for the association with LVD in a peritumoral hot spot were lymph node metastasis, histological grade and disease stage. The association with VEGF expression was similarly studied. LVD was detected by immunohistochemistry using D2-40.
  
  
  RESULTS
  LVD was significantly higher in lip cancer than in other oral tumors (P < 0.0001), while there were no significant differences of LVD among other cancers of the oral cavity. LVD tended to decrease with disease progression, increase of tumor size and increase of metastatic lymph node size. Eighty-four of 109 tumors were positive for VEGF-C or D. VEGF-C-positive tumor lesions were also positive for VEGF-D. Significantly higher levels of VEGF-C and D expressions were associated with large size of lymph node metastases (P = 0.02).
  
  
  CONCLUSIONS
  SCC of the oral region including the lip that produces VEGF-C and D is significantly more likely to cause cervical lymph node metastasis. LVD in a peritumoral hot spot does not directly indicate the risk of cervical lymph node metastasis, but instead may reflect lymphangiogenesis due to VEGF together with loss of lymphatic vessels through tumor growth and progression.
authors.affiliation: Division of Oral and Maxillofacial Biopathological Surgery, Department of Medicine of Sensory and Motor Organs, School of Medicine, Tottori University Faculty of Medicine, Yonago, 683-8504, Japan.
authors.forename: Soh
authors.initials: S
authors.lastname: Watanabe
authors.forename: Masako
authors.initials: M
authors.lastname: Kato
authors.forename: Isamu
authors.initials: I
authors.lastname: Kotani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ryoke
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
keywords: lip; lymphatic vessel density; oral cavity; squamous cell carcinoma; vascular endothelial growth factor
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