Hypoxia inducible factors 1α and 2α are associated with VEGF expression and angiogenesis in gallbladder carcinomas
Hypoxia inducible factors 1α and 2α are associated with VEGF expression and angiogenesis in gallbladder carcinomas
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DOI：
10.1002/jso.20443
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发表时间：
2006-09-01
影响因子：
2.5
通讯作者：
Koukourakis, M. I.
中科院分区：
文献类型：
--
作者：
Giatromanolaki, A.;Sivridis, E.;Koukourakis, M. I.
目的：探讨缺氧诱导因子HIF-1 α和HIF-2 α在胆囊腺癌组织中的意义及其与血管生成和VEGF表达的关系。方法：采用免疫组织化学方法对60例单独手术治疗的早期胆囊腺癌患者进行HIF-1 α和2 α的表达测定。同时检测血管密度（VD）、血管生成因子VEGF、胸苷磷酸化酶（TP）的表达。结果与临床病理特征及预后相关。结果：过表达HIF-1 α和2 α与肿瘤血管生成和VEGF表达增加显著相关，而HIF-2 α与TP上调相关。这些因素都与t分期和肿瘤分级无关。虽然hif与预后没有显著相关性，但HIF-1/2表达的患者未能开启VEGF或肿瘤内血管生成具有良好的预后。结论：缺氧诱导因子在胆囊腺癌组织中有较大比例表达上调，这与VEGF表达升高、血管生成增强密切相关。
Aims: To investigate the significance of the hypoxia inducible factors HIF-1 alpha and HIF-2 alpha in gallbladder adenocarcinomas and their relation to angiogenesis and to the expression of VEGF, an angiogenic factor transcriptionally regulated by HIF alpha s.Methods: HIF-1 alpha and 2 alpha expression was assessed immunohistochemically in 60 patients with early gallbladder adenocarcinomas, treated with surgery alone. In addition, the vascular density (VD) and the expression of the angiogenic factors VEGF and thymidine phosphorylase (TP) were examined. The results were correlated with clinico-pathological features and prognosis.Results: Overexpression of HIF-1 alpha and 2 alpha was significantly associated with increased tumor angiogenesis and VEGF expression, while HIF-2 alpha was linked with upregulation of TP. None of these factors were associated with T-stage and tumor grade. Although HIFs did not relate significantly with prognosis, patients with HIF-1/2 expression who failed to switch-on VEGF or intratumoral angiogenesis had a favorable outcome.Conclusion: Hypoxia inducible factors are upregulated in a large proportion of gallbladder adenocarcinomas, a feature strongly related to increased expression of VEGF and intensified angiogenesis.