ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy
ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy
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DOI：
10.1007/s00280-013-2181-2
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发表时间：
2013-07-01
影响因子：
3
通讯作者：
Frattini, Milo
中科院分区：
文献类型：
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作者：
De Dosso, Sara;Zanellato, Elena;Frattini, Milo
辅助化疗在可切除胃癌中发挥着越来越重要的作用。根据化疗敏感性定制化疗可能会改善结果，并且推定的预测分子标记物主要在亚洲患者中进行了评估。我们在欧洲队列中分析了关键的 DNA 和损伤信号传导因子，并将它们与结果相关联。对从接受基于顺铂的辅助化疗的胃癌患者的手术标本中获得的福尔马林固定的肿瘤样本进行了分析。采用免疫组织化学（IHC）分析切除修复交叉互补基因1（ERCC1）和胸苷酸合酶（TS）的表达，并通过直接测序检测p53突变。在招募的68名患者中，中位年龄为69岁（范围30-74岁），44名患者（65%）的UICC分期为III期。中位随访时间为 40.5 个月，无病生存期和总生存期分别为 18.0 (95% CI 13.4-22.76) 和 56 个月 (95% CI 44.87-67.13)。 67 例中 14 例 (21%) ERCC1 评分为 0，19 例中 1 例 (28%)，20 例中 2 例 (30%)，14 例中 3 例 (21%)。根据中值评分，经 IHC 分类为 ERCC1 阴性的患者的总生存期较长 (p = 0.04)。 67 例中 16 例 (24%) TS 评分为 0，27 例中 1 例 (40%)，16 例中 2 例 (24%)，8 例 (12%) 中 TS 评分为 3。 66 例病例中有 21 例 (32%) 发现 p53 突变。未发现 TS 和 p53 与结果相关。通过 IHC 进行的切除修复交叉互补基因 1 可能预测患者更有可能从根治性切除的胃癌中基于顺铂的辅助化疗中受益。对于出现 ERCC1 阳性肿瘤的患者，应评估替代方案。
Adjuvant chemotherapy is gaining an increasing role in resectable gastric cancer. Customizing chemotherapy on the basis of chemosensitivity may improve outcome, and putative predictive molecular markers have been mostly evaluated in Asian patients. We profiled key DNA and damage signaling factors and correlated them with outcome, in a European cohort.Formalin-fixed tumor samples obtained from surgical specimens of patients treated with adjuvant cisplatin-based chemotherapy for gastric cancer were analyzed. Immunohistochemistry (IHC) was performed to analyze excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TS) expression, and p53 mutations were detected with direct sequencing.Among the 68 patient recruited, the median age was 69 (range 30-74), and UICC stage was III in 44 patients (65 %). With a median follow-up of 40.5 months, disease-free and overall survival were 18.0 (95 % CI 13.4-22.76) and 56 months (95 % CI 44.87-67.13), respectively. ERCC1 score was 0 in 14 out 67 (21 %) cases, 1 in 19 (28 %), 2 in 20 (30 %) and 3 in 14 cases (21 %). Longer overall survival (p = 0.04) was found in patients categorized as ERCC1 negative by IHC according to median score. TS score was 0 in 16 out 67 (24 %) cases, 1 in 27 (40 %), 2 in 16 (24 %) and 3 in 8 cases (12 %). Mutations of p53 were found in 21 out 66 (32 %) cases. Neither TS nor p53 were found to correlate with outcome.Excision repair cross-complementing gene 1 by IHC might predict patients more likely to benefit from adjuvant cisplatin-based chemotherapy in curatively resected gastric cancer. In patients exhibiting ERCC1 positive tumors, alternative regimens should be evaluated.