APE1 and XRCC1 protein expression levels predict cancer-specific survival following radical radiotherapy in bladder cancer
APE1 and XRCC1 protein expression levels predict cancer-specific survival following radical radiotherapy in bladder cancer
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DOI：
10.1158/1078-0432.ccr-05-0045
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发表时间：
2005-09-01
影响因子：
11.5
通讯作者：
Kiltie, AE
中科院分区：
文献类型：
--
作者：
Sak, SC;Harnden, P;Kiltie, AE
前言：放射治疗为肌肉浸润性膀胱癌提供了保留膀胱的潜力，但仅有一部分肿瘤有反应，且尚无准确的预测方法。肿瘤细胞修复电离辐射引起的DNA损伤的能力影响辐射敏感性。因此，我们研究了DNA修复蛋白APE1和XRCC1在肌肉浸润性膀胱癌根治性放射治疗中的预后价值。材料和方法：对90例肌肉浸润性膀胱移行细胞癌患者的肿瘤进行APE1和XRCC1抗体免疫组织化学染色。结果：APE1和XRCC1的核染色中位数分别为98.7%(42.2-100%)和96.5%(0.6-99.6%)。Apl1和XRCC1的高表达水平(95%阳性)与患者癌症特异性生存率的改善有关(对数等级，分别P=0.02和0.006)。在多因素Cox回归模型中，APE1和XRCC1蛋白的表达以及肾积水是患者生存的唯一独立预测因素。结论：APE1和XRCC1蛋白的表达水平与放射治疗后的患者预后密切相关，将预后良好的患者与预后较差的50%患者(分别为82%和44%，3年病因特定生存率)分开。如果预期得到验证，这一简单的测试可以被纳入临床实践，以选择可能对放射治疗有反应的患者，并考虑对那些不太可能有反应的患者进行替代治疗。
Introduction: Radiotherapy offers the potential of bladder preservation in muscle-invasive bladder cancer, but only a proportion of tumors respond, and there are no accurate predictive methods. The ability of tumor cells to repair DNA damage induced by ionizing radiation influences radiosensitivity. We therefore investigated the prognostic value of the DNA repair proteins APE1 and XRCC1 in patients with muscle-invasive bladder cancer treated by radical radiotherapy.Materials and Methods: The tumors of 90 patients with muscle-invasive transitional cell carcinoma and known clinical outcomes were immunostained with APE1 and XRCC1 antibodies. Levels of protein expression were assessed as a percentage of tumor cells with positive nuclear staining (1,000 cells per tumor).Results:The median percentage of nuclear staining for APE1 was 98.7% (range, 42.2-100%) and for XRCC1 was 96.5% (range, 0.6-99.6%). High expression levels of APE1 or XRCC1 (95% positivity) were associated with improved patient cancer-specific survival (log-rank, P = 0.02 and 0.006, respectively). In a multivariate Cox regression model, APE1 and XRCC1 expression and hydronephrosis were the only independent predictors of patient survival.Conclusions: Expression levels of both APE1 and XRCC1 proteins were strongly associated with patient outcome following radiotherapy, separating patients with good outcome from the 50% with poor outcome (82% and 44%, 3-year cause-specific survival, respectively). If prospectively validated, this simple test could be incorporated into clinical practice to select patients likely to respond to radiotherapy and consider alternative forms of therapy for those unlikely to respond.