title: Impact of p16 status on pro- and anti-angiogenesis factors in head and neck cancers.
abstract: BACKGROUND
  Head and neck cancers (HNC) are aggressive tumours. Overexpression of p16 in HNC correlates with human papilloma virus (HPV)-associated HNC that carry a better prognosis than HPV-negative tumours. Angiogenesis is an important factor in tumour progression. Our aim was to dissect the impact of p16 expression on angiogenesis factors in HNC.
  
  
  METHODS
  Eighteen newly diagnosed HNC patients and controls were analysed. Eleven pro- and anti-angiogenesis factors were quantified using multiplex ELISA in HNC patients and controls. Angiogenesis factors were analysed in tumour tissue using immunohistochemistry.
  
  
  RESULTS
  Circulating levels of endostatin (anti-angiogenesis factor) were higher in the HNC group compared with healthy donors. Interestingly, the pro-angiogenesis factors angiopoietin-1 and vascular endothelial growth factor (VEGF) were significantly higher in patients with p16-negative compared with p16-positive HNC. Moreover, the major source of VEGF in p16-positive HNC tissue was tumour stromal cells. In contrast, both tumour cells and stromal cells expressed VEGF in p16-negative tissue.
  
  
  CONCLUSIONS
  We show that p16-negative tumours associate with increased circulating levels of pro-angiogenic VEGF and angiopoietin-1. Tissue expression of VEGF differs between p16-positive and p16-negative tumours. These findings may explain differences in the biological behaviour of p16-positive and p16-negative HNC. Better understanding of mechanisms by which the p16 status influences tumour angiogenesis may guide the development of targeted therapies.
authors.affiliation: 1] Department of ENT, St George's Hospital NHS Trust London, London, UK [2] Department of Oral and Maxillo-Facial Surgery, St George's Hospital NHS Trust London, London, UK [3] Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Baruah
authors.affiliation: Department of ENT, St George's Hospital NHS Trust London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Pathology, St George's Hospital NHS Trust London, London, UK.
authors.forename: P O G
authors.initials: PO
authors.lastname: Wilson
authors.affiliation: Department of ENT, St George's Hospital NHS Trust London, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Odutoye
authors.affiliation: Department of ENT, St George's Hospital NHS Trust London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Williamson
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, St George's Hospital NHS Trust London, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Hyde
authors.affiliation: Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Kaski
authors.affiliation: Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, UK.
authors.forename: I E
authors.initials: IE
authors.lastname: Dumitriu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000378:metabolism; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D043169:Endostatins / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D043169:Endostatins; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A