Clinicopathologic Significance of Hypoxia-Inducible Factor 1α Overexpression in Gastric Carcinomas

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Background:Hypoxia-inducible factor 1α (HIF-1α) plays a key role in responses to hypoxia and expression of HIF-1α downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1α expression in gastric carcinoma.Methods:We examined HIF-1α, 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-1α expression, clinicopathological features, and survival were examined.Results:HIF-1α 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-1α positive than in HIF-1α negative tumors and the 5-year survival rate was 58.4% for HIF-1α positive patients and 81.5% for HIF-1α negative patients (P=0.009). HIF-1α expression is an independent prognostic factor in gastric carcinoma (P=0.032).Conclusions:Overexpression of HIF-1α in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.

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