MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer.
MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer.
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DOI：
10.1158/0008-5472.can-10-1202
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发表时间：
2010-09-15
期刊：
影响因子：
11.2
通讯作者：
Kiltie AE
中科院分区：
文献类型：
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作者：
Choudhury A;Nelson LD;Teo MT;Chilka S;Bhattarai S;Johnston CF;Elliott F;Lowery J;Taylor CF;Churchman M;Bentley J;Knowles MA;Harnden P;Bristow RG;Bishop DT;Kiltie AE
在肌肉浸润性膀胱癌中，根治性放射治疗和手术的治愈率相似，但目前还不能预测哪种治疗方法对个别患者最有利。这项研究的主要目的是评估照射前采集的肿瘤样本中一组DNA损伤信号蛋白的表达是否可以作为放射治疗反应的预测标志，或者更确切地说，是预测预后的标志。应用免疫组织化学方法检测了两组膀胱癌根治性放疗患者和一组膀胱癌切除患者治疗前肿瘤标本中Mre11、Rad50、NBS1、ATM和H2 AX的蛋白表达。在放射治疗试验队列(n=86)中，Kaplan Meier分析显示，与高表达相比(43.1%对68.7%，p=0.012)，肿瘤mre11低表达与较差的癌症特异性生存率相关。这在放射治疗验证队列(n=93)中得到证实(43.0%比71.2%，p=0.020)。然而，在膀胱切除队列中(n=88)，mre11的表达与癌症特异性生存无关，这与mre11是一个预测标记物相称。联合放射治疗组中mre11高表达组的肿瘤特异性生存率明显好于高表达膀胱切除组(69.9%vs53.8%，p=0.021)。在这项经过验证的免疫组织化学研究中，Mre11蛋白的表达被证明并确认为与膀胱癌放射治疗后生存相关的预测因素，证明其纳入随后的试验设计是合理的。Mre11的表达最终可能使患者选择接受放射治疗或膀胱切除术，从而提高总体治愈率。
Radical radiotherapy and surgery achieve similar cure rates in muscle invasive bladder cancer, but the choice of which treatment would be most beneficial cannot currently be predicted for individual patients. The primary aim of this study was to assess whether expression of any of a panel of DNA damage signalling proteins in tumour samples taken before irradiation could be used as a predictive marker of radiotherapy response, or rather was prognostic. Protein expression of MRE11, RAD50, NBS1, ATM and H2AX was studied by immunohistochemistry in pre-treatment tumour specimens from two cohorts of bladder cancer patients (validation cohort prospectively acquired) treated with radical radiotherapy and one cohort of cystectomy patients. In the radiotherapy test cohort (n=86), low tumour MRE11 expression was associated with worse cancer-specific survival compared with high expression (43.1% versus 68.7% 3 year cause-specific survival, p=0.012) by Kaplan Meier analysis. This was confirmed in the radiotherapy validation cohort (n=93) (43.0% versus 71.2%, p=0.020). However, in the cystectomy cohort (n=88), MRE11 expression was not associated with cancer-specific survival, commensurate with MRE11 being a predictive marker. High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high expression cystectomy cohort (69.9% vs 53.8% 3 year cause-specific survival, p=0.021). In this validated immunohistochemistry study, MRE11 protein expression was demonstrated and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy, justifying its inclusion in subsequent trial design. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy, thus improving overall cure rates.