Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas
Clinicopathologic significance of hypoxia-inducible factor 1α overexpression in gastric carcinomas
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DOI：
10.1002/jso.20568
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发表时间：
2006-08-01
影响因子：
2.5
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Mizokami, Ken;Kakeji, Yoshihiro;Maehara, Yoshihiko
背景资料：缺氧诱导因子1 α（HIF-1 α）在对缺氧的反应中起关键作用，并且HIF-1 α下游基因的表达导致适应性代谢和增加的氧供应。方法：采用免疫组织化学方法检测126例胃癌组织中HIF-1 α、血管内皮生长因子（VEGF）和胰岛素样生长因子-2（IGF-2）的表达。通过免疫组化检测CD 34抗原水平以确定肿瘤内的微血管密度（MVD），并检测HIF-1 α表达、临床病理特征和生存率之间的相关性。HIF-1 α表达与肿瘤大小相关（P < 0.005）、浸润深度（P = 0.018）、VEGF表达（P = 0.03）和瘤内MVD（P < 0.005）。IGF-2在HIF-1 α阳性肿瘤中的表达比HIF-1 α阴性肿瘤中更普遍，HIF-1 α阳性患者的5年生存率为58.4%，HIF-1 α阴性患者的5年生存率为81.5%（P = 0.009）。结论：胃癌组织中HIF-1 α的过表达可能通过上调其下游基因产物的表达，促进VEGF介导的血管生成，从而导致胃癌患者预后不良。
Background: Hypoxia-inducible factor 1 alpha, (HIF-1 alpha) plays a key role in responses to hypoxia and expression of HIF-1 alpha downstream genes leads to both an adapted metabolism and increased oxygen supply. We investigated the clinical significance of HIF-1 alpha expression in gastric carcinoma.Methods: We examined HIF-1 alpha, 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-1 alpha expression, clinicopathological features, and survival were examined.Results: HIF-1 alpha 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-1 alpha positive than in HIF-1 alpha negative tumors and the 5-year survival rate was 58.4% for HIF-1 alpha positive patients and 81.5% for HIF-1 alpha negative patients (P = 0.009). HIF-1 alpha expression is an independent prognostic factor in gastric carcinoma (P = 0.032).Conclusions: Overexpression of HIF-1 alpha in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients.