title: Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer.
abstract: BACKGROUND
  Hypoxia is a common feature of rapidly growing solid tumors. Therefore, cellular adaptation to hypoxia and altered glucose metabolism are fundamental to the biology of cancer cells. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor for more than 60 genes recognized to control the delivery of oxygen and nutrients through the induction of angiogenesis and glycolysis under hypoxic conditions. Therefore, inhibition of the expression of HIF-1α can be expected to be potentially tumor-specific molecular target-based therapy. In this study, we evaluated the significance of HIF-1α expression in relationship to clinicopathological factors, prognosis, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD).
  
  
  METHODS
  Paraffin-embedded tumor specimens from 128 patients who underwent gastrectomy at Kurume University from 2004 to 2005 were used to assess the clinical significance of HIF-1α expression. We used the ABC method to perform an immunohistochemical analysis of the HIF-1α and VEGF expression.
  
  
  RESULTS
  Eighty-four (65.6%) of gastric cancer specimens were positive for HIF-1α expression. Multivariate analysis showed that histology, depth of invasion, VEGF expression, and MVD were significantly associated with HIF-1α expression. On relapse-free and overall survival curves, the HIF-1α-negative group was significantly higher than the HIF-1α-positive group. Moreover, HIF-1α(+)/VEGF(+) patients had the worst prognosis. HIF-1α expression was identified as a significant predictor of relapse-free survival and overall survival by multivariate Cox's proportional hazard analyses.
  
  
  CONCLUSIONS
  Overexpression of HIF-1α was found to be an indicator of poor prognosis for patients with gastric cancer and was significantly correlated with histology, depth of invasion, VEGF, and MVD.
authors.affiliation: Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Isobe
authors.forename: Keishiro
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Koufuji
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawahara
authors.forename: Tomoki
authors.initials: T
authors.lastname: Taira
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A