title: Metastasis via Peritumoral Lymphatic Dilation in Oral Squamous Cell Carcinoma.
abstract: OBJECTIVE
  Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics.
  
  
  METHODS
  Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation.
  
  
  RESULTS
  OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases.
  
  
  CONCLUSIONS
  In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University.
authors.forename: Han-Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Park
keywords: Lymphangiogenic factor; Lymphatic vessel density; Lymphatic vessel dilation; Nodal metastasis; Oral squamous cell carcinoma