Endogenous markers of two separate, hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial
Endogenous markers of two separate, hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial
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DOI：
10.1200/jco.2005.02.7474
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发表时间：
2006-02-10
影响因子：
45.3
通讯作者：
Harris, AL
中科院分区：
文献类型：
--
作者：
Koukourakis, MI;Bentzen, SM;Harris, AL
目的随机对照试验普遍显示加速放射治疗对头颈部鳞状细胞癌(HNSCC)有好处。然而，英国大型随机试验图表(连续超分割加速放射治疗)未能显示在918名HNSCC患者中强烈加速放射治疗(RT)的益处。在这项研究中，我们在CHART试验中调查了肿瘤缺氧对HNSCC患者预后的影响。有两种不同的低氧诱导因子(HIF)控制着不同的基因反应途径，我们用内源性低氧标志物HIF-2α(HIF-2)和HIF-1α(HIF-1)的指标碳酸氢酶CA9对它们进行评估。方法对918例患者中198例放疗前活检组织进行HIF-2和CA9的免疫组织化学分析。
Purpose Randomized controlled trials have generally shown a benefit from accelerated radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the large randomized United Kingdom trial CHART (Continuous Hyperfractionated Accelerated Radiotherapy) failed to show a benefit of strongly accelerated over standard radiotherapy (RT) in 918 patients with HNSCC. In this study, we investigated the impact of tumor hypoxia on the outcome of HNSCC patients in the CHART trial. There are two distinct hypoxia inducible factors (HIFs) that control different gene response pathways and we assessed them both with endogenous markers of hypoxia, hypoxia inducible factor HIF-2 alpha (HIF-2) and carbonic anhydrase CA9, an indicator of HIF-1 alpha (HIF-1) function.Methods Tissue from pre-RT biopsies performed in 198 of 918 patients recruited was analyzed for the immunohistochemical expression of HIF-2 and CA9.Results A significant association of high HIF2 and of high CA9 reactivity with poor locoregional control (P