Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
APMIS. 2010 Dec;118(12):941-8. doi: 10.1111/j.1600-0463.2010.02648.x. Epub 2010 Oct 25.
Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. Recent reports have suggested that ERCC1 is a predictive and prognostic marker in solid cancers treated with platinum-based chemotherapy. We performed this study to determine whether or not immunohistochemical expression of ERCC1 can predict objective tumor response and cancer-specific survival in patients with advanced urothelial carcinoma treated with cisplatin-based chemotherapy. We performed a retrospective analysis of 89 patients with advanced or recurrent urothelial cancer, who had undergone treatment at Samsung Medical Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89 patients with a known tumor response were available. ERCC1 expression was assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was positive in 49 patients (55%). The overall response rate after chemotherapy was 68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1-positive patients (p = 0.03); the difference in overall survival between patients with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not statistically significant. Other than ERCC1 expression, there was no independent prognostic factor for PFS. These results suggest a negative contribution by ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with cisplatin-based chemotherapy.
顺铂一直是尿路上皮癌化疗方案的基石。切除修复交叉互补基因 1（ERCC1）是负责核苷酸切除修复的铂-DNA 修复机制的关键组成部分。最近的报告表明，ERCC1 是接受铂类化疗的实体瘤中预测和预后的标志物。我们进行这项研究是为了确定 ERCC1 的免疫组织化学表达是否可以预测接受顺铂为基础的化疗的晚期尿路上皮癌患者的客观肿瘤反应和癌症特异性生存。我们对 2001 年 5 月至 2007 年 8 月在三星医疗中心接受治疗的 89 例晚期或复发性尿路上皮癌患者进行了回顾性分析。89 例已知肿瘤反应的患者均有治疗前活检样本。通过免疫组织化学评估 ERCC1 的表达。在 89 例患者中，49 例（55%）的 ERCC1 表达为阳性。化疗后的总反应率为 68.5%（95%CI54.8-74.8%）。在 61 例获得反应的患者中，27 例 ERCC-1 表达阴性，34 例阳性（p=0.61）。中位随访时间为 53.7 个月（范围 14.4-152.3 个月）。ERCC-1 阴性患者的无进展生存期（PFS）为 10.6 个月，ERCC-1 阳性患者为 8.4 个月（p=0.03）；ERCC-1 阴性肿瘤和 ERCC-1 阳性肿瘤患者的总生存期差异（p=0.73）无统计学意义。除 ERCC1 表达外，PFS 无其他独立预后因素。这些结果表明，在接受顺铂为基础的化疗的转移性尿路上皮癌患者中，ERCC1 表达对 PFS 有负面影响。
