title: Regional difference in intratumoral lymphangiogenesis of oral squamous cell carcinomas evaluated by immunohistochemistry using D2-40 and podoplanin antibody: an analysis in comparison with angiogenesis.
abstract: BACKGROUND
  Whether tumor cells induce lymphangiogenesis intratumorally or permeate pre-existing lymphatic vessels in the peritumoral area still remains unclear. In this study, we investigated in detail the intratumoral lymphangiogenesis of oral squamous cell carcinomas (SCC) in comparison with tumor angiogenesis.
  
  
  METHODS
  Immunohistochemistry with D2-40, podoplanin antibody, and CD34 antibody were used to evaluate the lymphatic vessel density (LVD) and blood microvessel density (MVD). Vascular endothelial growth factor (VEGF) and VEGF-C expressions of oral SCC were also assessed by immunohistochemistry.
  
  
  RESULTS
  LVD significantly increased in the superficial area of tumor tissue compared with normal mucosa, whereas it decreased in the deep area of intratumoral tissue near the invasion front, in sharp contrast to MVD, which significantly increased throughout tumor tissue. Consistent with the decreased intratumoral LVD and increased intratumoral MVD, VEGF-C expression of tumor cells was down-regulated in the deep area of tumor tissue, while VEGF expression of tumor cells was up-regulated throughout the tumor tissue.
  
  
  CONCLUSIONS
  Lymphangiogenesis in oral SCC varies depending on the region within the tumor tissue. It is not induced in the genuine tumor stroma near the invasion front, probably due to the down-regulation of VEGF-C expression of tumor cells, which is different from VEGF-mediated induction of intratumoral angiogenesis.
authors: The First Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
authors: Fumi
authors: F
authors: Ohno
authors: Hayao
authors: H
authors: Nakanishi
authors: Atsushi
authors: A
authors: Abe
authors: Yasushi
authors: Y
authors: Seki
authors: Atsutaka
authors: A
authors: Kinoshita
authors: Yasuhisa
authors: Y
authors: Hasegawa
authors: Masae
authors: M
authors: Tatematsu
authors: Kenichi
authors: K
authors: Kurita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000737:chemistry / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D000098853:Podoplanin
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C117468:PDPN protein, human; D000098853:Podoplanin; C500987:monoclonal antibody D2-40