title: Correlations of hypoxia-inducible factor-1α/hypoxia-inducible factor-2α expression with angiogenesis factors expression and prognosis in non-small cell lung cancer.
abstract: BACKGROUND
  Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer (NSCLC).
  
  
  METHODS
  In the current work we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed.
  
  
  RESULTS
  High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases, respectively. There was no direct correlation between HIF-1α and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2α (P = 0.007), and we also found a significant correlation between HIF-2α and T or N stage (P = 0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (P = 0.084), which showed a higher expression in early stage tumors. A significant correlation (P = 0.045) was noticed between HIF-1α and vascular endothelial growth factor (VEGF) expression while the expression levels of thymidine phosphorylase (TP), cyclooxygenase (COX)-2 and microvessel density (MVD) were significantly higher in high HIF-2α tumors (P = 0.020, 0.004, and 0.046, respectively). In addition, univariate analysis of overall survival demonstrated that HIF-2α expression, but not HIF-1α, was related to poor outcome (P = 0.001) and it retained significant in multivariate analysis (P = 0.036).
  
  
  CONCLUSIONS
  Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC.
authors.affiliation: Division of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Wu
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Kai
authors.initials: K
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D013939:Thymidine Phosphorylase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D043925:Angiogenesis Inducing Agents; D051792:Basic Helix-Loop-Helix Proteins; D051546:Cyclooxygenase 2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013939:Thymidine Phosphorylase; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1