中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (7): 522-528.doi: 10.3969/j.issn.1007-3969.2015.07.006

• 论著 • 上一篇    下一篇

微卫星不稳定状态对Ⅳ期结直肠癌患者化疗反应性和预后的影响

吴宇辰1,张长胜2,梁斐3,黄丹4,朱骥3,5,徐烨1,刘方奇1   

  1. 1. 复旦大学附属肿瘤医院大肠外科,复旦大学上海医学院肿瘤学系,上海 200032 ;
    2. 合肥市第二人民医院胃肠外科,安徽 合肥 230011 ;
    3. 复旦大学附属肿瘤医院临床统计中心,复旦大学上海医学院肿瘤学系,上海 200032 ;
    4. 复旦大学附属肿瘤医院病理科,复旦大学上海医学院肿瘤学系,上海 200032 ;
    5. 复旦大学附属肿瘤医院放疗科,复旦大学上海医学院肿瘤学系,上海 200032
  • 出版日期:2015-07-30 发布日期:2015-12-09
  • 通信作者: 刘方奇 E-mail:liufq021@163.com

Prognostic value and sensitivity to chemotherapy of microsatellite instability in advanced colorectal cancer

WU Yuchen1, ZHANG Changsheng2, LIANG Fei3, HUANG Dan4, ZHU Ji3,5, XU Ye1, LIU Fangqi1   

  1. 1.Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Department of Gastrointestinal Surgery, the Second People’s Hospital of Hefei City, Hefei Anhui 230011, China; 3. Clinical Statistical Center, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 4. Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 5. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Published:2015-07-30 Online:2015-12-09
  • Contact: LIU Fangqi E-mail: liufq021@163.com

摘要: 背景与目的:错配修复缺陷导致的微卫星不稳(microsatellite inistability,MSI)状态对Ⅱ、Ⅲ期结直肠癌患者的预后及化疗敏感性有重要作用,但在晚期肠癌中研究较少。该研究探讨微卫星不稳对晚期结直肠癌患者化疗敏感性及预后的影响。方法:收集采用XELOX或FOLFOX为一线化疗方案的Ⅳ期肠癌患者的原发肿瘤组织,免疫组化方法检测肿瘤组织中错配修复基因hMLH1、hMSH2、hMSH6和hPMS2的蛋白表达,分析微卫星状态与患者临床特征、预后及化疗反应的相关性。结果:共收集113例晚期结直肠癌患者,未发现MSI与患者总体生存时间(overall survival,OS)以及化疗敏感性存在相关。亚组分析中我们发现79例原发灶姑息性切除的患者中,MSI 患者(22例)较MSS患者(57例)的中位无疾病进展时间(progression-free survival,PFS)明显延长(19.9个月 vs 7个月,P=0.005),但MSI与OS无关(P=0.07)。对该79例患者预后行Cox多因素分析显示,MSI是影响患者PFS的独立危险因素(P=0.043,MSS/MSI,HR=2.079)。此外,该群患者的MSI状态与疾病控制率(59.1% vs31.6%,P=0.025)相关。结论:在原发灶姑息性切除的Ⅳ期结直肠癌患者中,微卫星不稳定状态与无疾病进展时间和化疗的疾病控制率呈正相关,因而有必要对该群患者进行微卫星检测。

关键词: 晚期结肠直肠癌, 微卫星不稳定, 化疗, 预后

Abstract: Background and purpose: Microsatellite instability (MSI) status is commonly applied to predict the prognosis and chemosensitivity in stage Ⅱ and stage Ⅲ colorectal cancer patients. However, researches of its function on metastasis colorectal cancer are limited. This study investigated its value on prognosis and chemosensitivity in metastatic colorectal cancer (CRC) patients. Methods: We retrospectively investigated tumor tissues from metastasis CRC patients who were treated with oxaliplatin and 5-FU-based therapy regimens (FOLFOX and XELOX). Immunostaining of proteins of the mismatch repair gene hMLH1, hMSH2, hMSH6 and hPMS2 was performed. Prognostic value and chemosensitivity in patients with MSI status were also determined. Results: Clinical features from 113 patients were analyzed. No correlation of overall survival (OS) and chemosensitivity with MSI status was found. We further investigated 79 patients with synchronous metastasis and palliatively tumor resection. Median progression free survival (PFS) from 22 MSI patients was significant longer than that in 57 MSS patients (19.9 months vs 7 months, P=0.005). No significant difference was seen in OS comparison (P=0.07). MSI status was also an independent prognostic factors of PFS by Cox multivariate analysis (MSS/ MSI,HR=2.079, P=0.043). Moreover, in this group, MSI patients had improved disease control rate (59.1% vs 31.6%, P=0.025) in chemosensitivity analysis than MSS patients. Conclusion: A better PFS in MSI patients with synchronous metastasis and palliative tumor resection was found after treated with oxaliplatin and 5-FU-based therapy and a better chemosensitivity in MSI patients was also found.

Key words: Advanced colorectal cancer, Microsatellite instability, Chemotherapy, Prognosis