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首页> 外文期刊>British Journal of Cancer >GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON
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GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

机译：GLUT1和CAIX作为缺氧性膀胱癌的内在标志物：与血管和增殖的关系作为ARCON预后的指标

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Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5?g?m?2 pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P=0.0001) for GLUT1 and 0.74 (P<0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.
机译：葡萄糖转运蛋白1蛋白（GLUT1）和碳酸酐酶IX（CAIX）受缺氧诱导因子1（HIF-1）的调节，并已被研究作为缺氧的假定内在细胞标志物。这项研究直接比较了CAIX和GLUT1与吡莫硝唑的结合在一组预期的膀胱癌患者中的应用，并且还研究了这些标志物与血管生成和增殖相结合的预后意义，在一项回顾性膀胱癌II期临床研究中使用碳原和烟酰胺（ARCON）进行的放射疗法。总共21例诊断为膀胱移行细胞癌的患者接受0.5？g？m？2哌莫尼唑。对系列肿瘤切片进行吡莫硝唑，GLUT1和CAIX染色并进行比较。从先前使用ARCON治疗过浸润性膀胱癌的64例患者获得的组织切片对GLUT1和CAIX以及Ki-67和CD31 / 34进行染色。内在标记与吡莫尼唑的地理共定位性良好，个体患者的一致性很高。 GLUT1的相关系数为0.82（P = 0.0001），CAIX的相关系数为0.74（P <0.0001）。在这两组患者中，内在缺氧标记物彼此高度相关，并且在回顾性研究中也与增殖相关。在单变量和多变量分析中，GLUT1和CAIX是总体生存率和特定生存率的独立预测因子。低氧标记物不能预测局部控制或无转移生存，尽管较高的Ki-67指数显示了局部衰竭的趋势。数据表明，低氧调节和加速治疗可能是膀胱癌的有效治疗选择。

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