title: Immunohistochemical study of the angiogenetic network of VEGF, HIF1α, VEGFR-2 and endothelial nitric oxide synthase (eNOS) in human breast cancer.
abstract: BACKGROUND
  The role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse. The aim of the current study was to investigate the expression of key molecules involved in these opposite pathways in primary breast cancer.
  
  
  METHODS
  Representative tumor samples from 242 patients with early-stage breast cancer (invasive ductal breast carcinomas) were investigated for the expression of VEGF, VEGFR-2, HIF1α, iNOS, and eNOS using immunohistochemistry.
  
  
  RESULTS
  Endothelial NOS was found in 159 cases, VEGF in 131 cases, HIF-1α in 139 cases, VEGFR2 in 185 cases and inducible NOS (iNOS) in 22 cases. There was a significant correlation between the expression of VEGF and VEGFR-2, eNOS and VEGF, eNOS and VEGFR-2, eNOS and HIF1α. No statistically significant correlation was found between iNOS and the rest of the studied molecules.
  
  
  CONCLUSIONS
  In breast cancer cases, the major molecules regulating NO and VEGF production can be co-expressed in the individual carcinomas implying a possibility for the relevant pathways to be active; however appropriate functional experiments remain to be conducted to prove such a hypothesis.
authors.affiliation: Department of Pathology, Medical School of the University of Crete, Voutes, Heraklion, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kafousi
authors.forename: Thomas
authors.initials: T
authors.lastname: Vrekoussis
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Tsentelierou
authors.forename: Kitty
authors.initials: K
authors.lastname: Pavlakis
authors.forename: Iordanis
authors.initials: I
authors.lastname: Navrozoglou
authors.forename: Vassilios
authors.initials: V
authors.lastname: Dousias
authors.forename: Elias
authors.initials: E
authors.lastname: Sanidas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsiftsis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
mesh_terms: D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism*; D016009:Chi-Square Distribution; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D040301:Vascular Endothelial Growth Factor Receptor-2