title: Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer.
abstract: BACKGROUND
  The cause of preferential metastatic spreading to cervical lymph nodes in oral squamous cell cancer (SCC) is not quite clear. As the density of microvessels may influence the metastatic behaviour, we were interested in how the density of blood/lymphatic microvessels are related to primary SCC and the clinical course of the disease.
  
  
  METHODS
  Lymphatic and blood microvessels of 28 patients with oral SCC were identified immunohistochemically by antibodies against podoplanin and CD34, respectively. Lymphatic microvessel density (LVD) and blood microvessel density (MVD), and the expression of VEGF-C were determined. These findings were compared with the long-term clinicopathological data of the patients.
  
  
  RESULTS
  LVD and MVD were significantly higher than in control tissues. The amount of lymphatic microvessels correlated positively with the expression of VEGF-C, the tumour grade, the nodal status and with later appearing metastasis. The latter three parameters, however, did not influence the clinical course of the disease.
  
  
  CONCLUSIONS
  VEGF-C expression in oral SCC triggers lymphatic angiogenesis, which may result in a higher risk for cervical lymph node metastasis. The angiogenetic effect of VEGF-C may also favour the onset of late lymphatic and haematogenous metastases.
authors.affiliation: Department of Pathology, University Hospital Vienna, Währinger Gürtel 8-20, A-090 Vienna, Austria. roland.sedivy@akh-wien.ac.at
authors.forename: Roland
authors.initials: R
authors.lastname: Sedivy
authors.forename: Johann
authors.initials: J
authors.lastname: Beck-Mannagetta
authors.forename: C
authors.initials: C
authors.lastname: Haverkampf
authors.forename: Walter
authors.initials: W
authors.lastname: Battistutti
authors.forename: Selma
authors.initials: S
authors.lastname: Hönigschnabl
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology* / Q000556:secondary; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008208:Lymphatic System / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000098:blood supply / Q000473:pathology*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D015996:Survival Rate; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis*; D000098853:Podoplanin
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D008562:Membrane Glycoproteins; D042582:Vascular Endothelial Growth Factor C; C117468:PDPN protein, human; D000098853:Podoplanin