Prognostic Value of ERCC1, Thymidylate Synthase, and Glutathione S-Transferase π for 5-FU/Oxaliplatin Chemotherapy in Advanced Colorectal Cancer
Prognostic Value of ERCC1, Thymidylate Synthase, and Glutathione S-Transferase π for 5-FU/Oxaliplatin Chemotherapy in Advanced Colorectal Cancer
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DOI：
10.1097/coc.0b013e31817be58e
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发表时间：
2009-02-01
影响因子：
2.6
通讯作者：
Kim, Hyo-Jin
中科院分区：
文献类型：
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作者：
Kim, Sung-Hyun;Kwon, Hyuk-Chan;Kim, Hyo-Jin
背景：本研究的目的是确定切除修复交叉互补1 （ERCC1）、胸苷酸合成酶（TS）和谷胱甘肽s-转移酶pi （GST pi）的表达是否预测晚期结直肠癌患者接受氟尿嘧啶(5-FU)/奥沙利铂化疗的临床结局。方法：研究人群包括70例晚期结直肠癌患者（中位年龄54岁）。患者在第1天接受奥沙利铂85 mg/m(2) 2小时输注治疗，加上亚叶酸素（LV） 20 mg/m(2)超过10分钟，随后5-FU灌注400 mg/m(2)，从第1天到第2天连续输注600 mg/m(2) 22小时。每隔2周重复治疗一次。免疫组化检测ERCC1、TS和GST pi在原发肿瘤中的表达。结果：ERCC1、TS、GST pi阳性率为55.7%。分别占68.6%和71.4%。无TS表达的患者更容易对化疗产生反应（P = 0.009）。治疗反应与ERCC1或GST pi表达谱无显著差异（P = 0.768, P = 0.589）。无ERCC1表达患者的中位总生存期（OS）显著延长（P = 0.0474）。ERCC1阳性合并TS阳性或ERCC1阳性合并TS阳性、GST pi阳性患者的OS较差（P = 0.0017, P = 0.0323）。多因素分析显示ERCC I和TS表达均显著影响OS（风险比1.72,P = 0.023）。结论：ERCC1和TS的免疫组化研究可能有助于预测5-FU联合奥沙利铂治疗的晚期结直肠癌患者的临床预后。
Background: The aim of this study was to determine whether the expression of the excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS) and glutathione S-transferase pi (GST pi) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy.Methods: The study population consisted of 70 patients with advanced colorectal cancer (median age, 54 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on days 1 plus leucovorin (LV) 20 mg/m(2) over 10 minutes, followed by 5-FU bolus 400 mg/m(2) and a 22-hour continuous infusion of 600 mg/m(2) from day 1 to 2. Treatment was repeated at 2-week intervals. The expression of ERCC1, TS, and GST pi in primary tumors was examined using immunohistochemistry.Results: ERCC1, TS, and GST pi were positive in 55.7%. 68.6%, and 71.4% of cases, respectively. Patients without TS expression were more likely to respond to chemotherapy (P = 0.009). There were no significant differences between response to treatment and the ERCC1 or GST pi expression pattern (P = 0.768, P = 0.589, respectively). The median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0474). Patients who were ERCC l positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GST pi, positive had a poor OS (P = 0.0017, P = 0.0323, respectively). Multivariate analysis revealed that both ERCC I and TS expression significantly impacted OS (hazard ratio 1.72, P = 0.023).Conclusion: Immunohistochemical study of ERCC1 and TS may be useful for the prediction of clinical outcome in patients with advanced colorectal cancer treated with 5-FU and oxaliplatin.