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Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy


中 国普 外基 础与 临床 杂志
普外科学新知栏目
题目
辅助疗法后大肠癌简单重复序列不稳定的临床影响

电子版供稿单

Title 来源 Resources 原文发布日期 24/12/2009 Date 由于对出现 MMR 缺陷的大肠癌的研究在临床和病理学两方面都有重 供稿内容 Kim Contents 大意义,且目前对于将 p53 作为大肠癌预测标志并没有达成共识, ST
等 人 讨 论 了 对 于 MSI-H/MMR-D 和 p53 在 oxaliplatin/5-FU/leucovorin,FOLFOX 辅助疗法的进行 R0 切除结肠癌患 者中的临床应用。他们分析了 135 个都在进行 R0 后接受了含 5-FU 和 奥沙利铂的辅助化疗的病人样本。结果显示在接受 FOLFOX 辅助化疗 的患者中 MMR 状况和 DFS(P=0.56) OS(P=0.61) 或 没有明显关系。 p53 状况对 DFS(P=0.11)和 OS(P=0.94)也无明显影响。对于基因分型 和 IHC 检测结果一致的患者(样本容量 108) ,其样本的 DFS(P=0.57) 和 OS(P=0.98)与 MSI-H/MMR-D 型以及 MSI-L/S/MMR-I 型肿瘤并无 差异。他们的结论是 MMR 状况或 p53 阳性状况与患者接受 FOLFOX 辅助化疗的后果并无明显关联。在辅助化疗中加入奥沙利铂可能克服 5-FU 对于 MSI-H/MMR-D 型癌症的不良效应。 Clinical impact of microsatellite instability in colon cancer following Cancer Chemother Pharmacol.2010;66(4):659-67.

原文题目 Title

adjuvant FOLFOX therapy

原文摘要 PURPOSE: Abstract (全文请以 PDF 格式打 全文请以 Colon cancer with DNA mismatch repair (MMR) defects reveals 包发送) 包发送
indistinguishable clinical and pathologic aspects, including better prognosis and reduced response to 5-fluorouracil (5-FU)-based chemotherapy. There has been no consensus for p53 as a prognostic marker in colorectal cancer. This study investigated the clinical implication of MSI-H/MMR-D and p53 expression in R0-resected colon cancer patients who received adjuvant oxaliplatin/5-FU/leucovorin (FOLFOX) therapy. EXPERIMENTAL DESIGN:

We analyzed 135 patients, who had been treated by adjuvant chemotherapy containing 5-FU and oxaliplatin (FOLFOX) after curative resection (R0) for colon adenocarcinoma between May 2004 and November 2007. Tumor expression of the MMR proteins, MLH1 and MSH2, was detected by immunohistochemistry (IHC) in surgically resected tumor specimens. MSI was analyzed by polymerase chain reaction (PCR) amplification using fluorescent dye-labeled primers specific for microsatellite loci. Tumors with MMR defects were defined as those demonstrating loss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype. Expression patterns of p53 were determined in a semiquantitative manner by light microscopy. RESULTS: There were 13 (9.6%) patients with stage II, 108 (80%) with stage III, and 14 (10.4%) with stage IV. Fourteen patients with stage IV (10.3%) had metastases to liver only, all of whom underwent complete metastasectomy for liver metastases. In total, 134 tumor specimens were genotyped, 115 specimens were tested by IHC and 113 cases had both genotyping and IHC results available for analysis. Genotyping results demonstrated that 12 (9.0%) cases were MSI-H and 122 (91.0%) were MSI-L/S. By IHC, 11 (9.6%) patients were MMR-D and 104 (90.4%) were MMR-I. The methods were in agreement in 108 patients (94.7%). We assessed 114 patients for p53 expression by immunostaining. MMR status was not significantly

associated with DFS (P = 0.56) or OS (P = 0.61) in patients with colon cancer (n = 135) receiving adjuvant FOLFOX. According to p53 status, there was also no significant difference for DFS (P = 0.11) and OS (P = 0.94). For patients with genotyping/IHC agreement (n = 108), there was no difference in DFS (P = 0.57) and OS (P = 0.98) between patients with MSI-H/MMR-D and MSI-L/S/MMR-I tumors. CONCLUSION: The MMR status or p53 positivity was not significantly associated with outcomes to FOLFOX as adjuvant chemotherapy in colon cancer patients with R0 resection. Adding oxaliplatin in adjuvant chemotherapy may overcome negative impact of 5-FU on colon cancers with MSI-H/MMR-D.

全文摘要翻译 Abstract translation

目标: 目标 对出现 DNA 错配修复 (MMR) 缺陷的大肠癌的研究在临床和病理学两 方面都有重大意义,包括更好的预测和降低 5-氟尿嘧啶(5-FU)化疗的 反应。目前对于将 p53 作为大肠癌预测标志并没有达成共识。本研究探 讨了对于 MSI-H/MMR-D 和 p53 在接受奥沙利铂/5-氟尿嘧啶化疗/亚叶 酸钙(oxaliplatin/5-FU/leucovorin,FOLFOX)辅助疗法的进行 R0 切除结 肠癌患者中的临床应用。 实验设计: 实验设计: 我们分析了 2004 年五月到 2007 年十一月间的 135 个病人样本, 他们都 在进行大肠癌治愈性切除(R0)后接受了含 5-FU 和奥沙利铂的辅助化 疗。MMR 蛋白,MLH1 和 MSH2 在肿瘤中的表现型通过对术后切除的 肿瘤样本进行免疫组织化学染色 (immunohistochemistry,IHC) 加以检测。 利用 简单重复 序列基因位点 专用荧光 标记底物对聚 合酶链式 反应 (PCR)放大进行对 MSI 的分析。那些显示缺乏 MMR 蛋白表现 (MMR-D)或者是高简单重复序列不稳定(MSI-H)基因型的肿瘤即 为存在 MMR 缺陷的肿瘤。 表现型由光学显微镜的半定量观测确定。 P53 结果: 结果: 样本中 13 名(9.6%)患者处于 II 阶段,108 名(80%)处于 III 阶段, 还有 14 名(10.4%)处于 IV 阶段。14 名处于 IV 阶段的患者都只存在 肝脏转移,他们都进行了完全的肝脏转移瘤切除。实验确定了 134 个肿 瘤样本的基因型, 进行了 115 个样本的 IHC 测试, 最终共有 113 个样本 具有这两项实验的数据可加以分析。基因分型结果显示 12 项(9.0%)

样本为 MSI-H 基因型,其余 122 项(91.0%)为 MSI-L/S。IHC 结果显 示,11 位(9.6%)患者为 MMR-D 表现型而其余 104 名(90.4%)为 MMR-I。两项检测结果对于 108 名(94.7%)患者是一致的。我们通过 免疫组化对 114 名患者的 p53 表现进行了检测。在接受 FOLFOX 辅助 化疗的大肠癌患者(样本容量 135)中 MMR 状况和无病生存期(DFS, P=0.56)或总生存期(OS,P=0.61)没有明显关系。从 p53 检测结果看, p53 状况对 DFS(P=0.11)和 OS(P=0.94)也无明显影响。对于基因分 型和 IHC 检测结果一致的患者 (样本容量 108) 其样本的 DFS , (P=0.57) 和 OS(P=0.98)与 MSI-H/MMR-D 型以及 MSI-L/S/MMR-I 型肿瘤并无 差异。 结论: 结论: MMR 状况或 p53 阳性状况与在接受 R0 切除的大肠癌患者接受 FOLFOX 辅助化疗的后果并无明显关联。 在辅助化疗中加入奥沙利铂可 能克服 5-FU 对于 MSI-H/MMR-D 型癌症的不良效应。

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供稿时间

凌晨

Update

11/3/2012


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