Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
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DOI：
10.1093/annonc/mdl430
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发表时间：
2007-03-01
影响因子：
50.5
通讯作者：
Kim, H. -J.
中科院分区：
文献类型：
--
作者：
Kwon, H. -C.;Roh, M. S.;Kim, H. -J.
背景：本研究的目的是确定切除修复交叉互补 (ERCC1)、胸苷酸合酶 (TS) 和谷胱甘肽 S-转移酶 P1 (GSTP1) 的表达是否可以预测接受氟尿嘧啶 (5-氟尿嘧啶)/奥沙利铂化疗的晚期胃癌患者的临床结果。 患者和方法：研究人群包括 64 名晚期胃癌患者（中位年龄 51 岁）。患者在第1天接受奥沙利铂85 mg/m(2) 2小时输注，加甲酰四氢叶酸20 mg/m(2)治疗10分钟以上，随后5-FU推注400 mg/m(2)，并在第1-2天连续输注600 mg/m(2) 22小时。以两周为间隔重复治疗。免疫组化检测原发灶ERCC1、TS、GSTP1的表达。结果：ERCC1、TS、GSTP1的阳性率分别为70.3%、29.7%、50.0%。无 ERCC1 表达的患者更有可能对化疗产生反应（P = 0.045）。反应与 TS 或 GSTP1 表达模式之间没有显着差异（分别为 P = 0.813、P = 0.305）。无 ERCC1 表达的患者的中位总生存期 (OS) 显着更长 (P = 0.0396)。 TS 或 GSTP1 表达与生存无关（分别为 P = 0.4578、P = 0.8121）。多变量分析显示，ERCC1 表达对 OS 有显着影响（风险比 1.92，P = 0.037）。结论：ERCC1 的免疫组织化学研究可能有助于预测接受 5-FU 和奥沙利铂治疗的晚期胃癌患者的临床结果。
Background: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy.Patients and methods: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion at day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by 5-FU bolus 400 mg/m(2) and 22-h continuous infusion of 600 mg/m(2) at days 1-2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry.Results: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037).Conclusion: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.