Clinicopathologic significance of hypoxia-inducible factor 1alpha overexpression in gastric carcinomas

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.