title: Clinicopathologic significance of hypoxia-inducible factor 1alpha overexpression in gastric carcinomas.
abstract: BACKGROUND
  Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a key role in responses to hypoxia and expression of HIF-1alpha downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1alpha expression in gastric carcinoma.
  
  
  METHODS
  We examined HIF-1alpha, vascular endothelial growth factor (VEGF), and insulin-like growth factor-2 (IGF-2) expression patterns immunohistochemically in 126 specimens of gastric carcinoma. CD34 antigen levels were also examined by immunohistochemistry to determine microvessel density (MVD) within tumors and correlations between HIF-1alpha expression, clinicopathological features, and survival were examined.
  
  
  RESULTS
  HIF-1alpha expression correlated with tumor size (P<0.005), depth of invasion (P=0.018), VEGF expression (P=0.03), and intra-tumor MVD (P<0.005). IGF-2 expression was more prevalent in HIF-1alpha positive than in HIF-1alpha negative tumors and the 5-year survival rate was 58.4% for HIF-1alpha positive patients and 81.5% for HIF-1alpha negative patients (P=0.009). HIF-1alpha expression is an independent prognostic factor in gastric carcinoma (P=0.032).
  
  
  CONCLUSIONS
  Overexpression of HIF-1alpha in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, and Department of Pathology, Saga Prefectural Hospital Koseikan, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Mizokami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Shinya
authors.initials: S
authors.lastname: Oda
authors.forename: Koji
authors.initials: K
authors.lastname: Irie
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yonemura
authors.forename: Fumio
authors.initials: F
authors.lastname: Konishi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005743:Gastrectomy; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D007335:Insulin-Like Growth Factor II