ERCC1 as a Prognostic and Predictive Biomarker for Urothelial Carcinoma of the Bladder following Radical Cystectomy
ERCC1 as a Prognostic and Predictive Biomarker for Urothelial Carcinoma of the Bladder following Radical Cystectomy
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DOI：
10.1016/j.juro.2015.06.099
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发表时间：
2015-11-01
影响因子：
6.6
通讯作者：
Shariat, Shahrokh F.
中科院分区：
文献类型：
--
作者：
Klatte, Tobias;Seitz, Christian;Shariat, Shahrokh F.
目的：ERCC 1是核苷酸切除修复途径的关键酶，维持基因组的稳定性。ERCC 1已被提出作为膀胱尿路上皮癌患者的预后和预测的生物标志物，但有有限的数据根治cycloplastic.Materials和方法：ERCC 1在根治性cycloplastics. Materials的患者进行了评估，免疫组化。评估了与无病生存期和癌症特异性生存期的关系，以及基于顺铂的辅助化疗的效果。结果：308例（71.3%）膀胱移行细胞癌中ERCC 1表达阳性;与临床病理学变量无相关性（均p >0.3）。中位术后随访时间为128个月。在多变量分析中，ERCC 1阳性肿瘤患者的无病生存率（HR 0.70，p = 0.028）和癌症特异性生存率（HR 0.70，p = 0.032）显著优于ERCC 1阴性肿瘤患者。在纳入ERCC 1后，多变量模型的区分度增加了0.7%至0.9%。ERCC 1状态未改变基于顺铂的辅助联合化疗的效果（分别为p = 0.38和0.88）。ERCC 1与顺铂敏感性无相关性（R-2 = 0.02，p = 0.46）。结论：ERCC 1可能是膀胱尿路上皮癌的一个预后指标。ERCC 1阳性肿瘤患者的生存率可能高于ERCC 1阴性肿瘤患者。然而，基于顺铂的辅助化疗的疗效似乎与ERCC 1状态无关。
Purpose: ERCC1 is the key enzyme of the nucleotide excision repair pathway, which maintains genomic stability. ERCC1 has been proposed as a prognostic and predictive biomarker for patients with urothelial carcinoma of the bladder but there are limited data on patients after radical cystectomy.Materials and Methods: ERCC1 was evaluated by immunohistochemistry in radical cystectomy specimens of 432 patients. Associations with disease-free and cancer specific survival, and the effect of adjuvant cisplatin based chemotherapy were assessed. Further, ERCC1 mRNA expression and in vitro sensitivity to cisplatin were correlated in 25 bladder urothelial carcinoma cell lines.Results: ERCC1 was expressed in 308 tumors (71.3%). There was no association with clinicopathological variables (each p >0.3). Median postoperative followup was 128 months. On multivariable analyses patients with ERCC1 positive tumors had significantly better disease-free survival (HR 0.70, p = 0.028) and cancer specific survival (HR 0.70, p = 0.032) than those with ERCC1 negative tumors. Discrimination of the multivariable models increased by 0.7% to 0.9% following the inclusion of ERCC1. There was no modification of the effect of adjuvant cisplatin based combination chemotherapy by ERCC1 status (p = 0.38 and 0.88, respectively). There was also no correlation between ERCC1 and sensitivity to cisplatin in vitro (R-2 = 0.02, p = 0.46).Conclusions: ERCC1 may be a prognostic biomarker for urothelial carcinoma of the bladder. Patients with ERCC1 positive tumors may have better survival than those with ERCC1 negative tumors. However, the efficacy of adjuvant cisplatin based chemotherapy appears to be unrelated to ERCC1 status.