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结直肠癌原发灶与转移灶K-ras基因突变的比较分析
引用本文:谭聪,倪淑娟,翁微微,黄丹,盛伟琪,廉朋.结直肠癌原发灶与转移灶K-ras基因突变的比较分析[J].中国癌症杂志,2013,23(10):829-833.
作者姓名:谭聪  倪淑娟  翁微微  黄丹  盛伟琪  廉朋
作者单位:1.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; 2.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
基金项目:上海市卫生局青年科研项目(No:2008Y079)
摘    要:背景与目的:K-ras基因突变是抗表皮生长因子受体(epidermal growth factor receptor,EGFR)靶向治疗的重要负性预测因子。本研究拟对结直肠癌原发灶与转移灶中K-ras基因状态的一致性进行比较,以探讨目前临床K-ras检测的科学性与严谨性。方法:收集复旦大学附属肿瘤医院手术切除的结直肠癌原发灶及转移灶石蜡包埋组织76对,提取DNA,经过PCR扩增后,对产物进行基因序列分析,检测结直肠癌中K-ras基因外显子2基因序列。结果:76例患者中有15例结直肠癌原发灶与转移灶的K-ras基因突变情况不一致。76例结直肠癌原发灶有31例发生突变,突变率为40.8%,其中第13号密码子突变16例,第12号密码子突变15例;76例结直肠癌转移灶有31例发生突变,突变率为40.8%,其中第13号密码子突变15例,第12号密码子突变16例。结论:结直肠癌原发灶和转移灶中K-ras基因状态并不一致,且存在19.7%的表达差异率,提示通过检测原发灶K-ras基因表达状态来确定针对转移灶的西妥昔单克隆抗体药物选择存在不严谨性,需要进一步完善。

关 键 词:结直肠癌  K-ras基因  原发灶  转移灶  西妥昔单抗  

Evaluation of K-ras status concordance between primary colorectal cancer and related metastatic sites
TAN Cong,NI Shu-juan,WENG Wei-wei,HUANG Dan,SHENG Wei-qi,LIAN Peng.Evaluation of K-ras status concordance between primary colorectal cancer and related metastatic sites[J].China Oncology,2013,23(10):829-833.
Authors:TAN Cong  NI Shu-juan  WENG Wei-wei  HUANG Dan  SHENG Wei-qi  LIAN Peng
Affiliation:1. Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China;  2. Department of Colorectal Cancer Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Abstract:Background and purpose: Metastatic colorectal cancer (mCRC) patients with K-ras mutation won’t benefit in the anti-epidermal growth factor receptor (EGFR) treatments. Thus K-ras mutation analysis is mandatory before this treatment. There is controversy that K-ras mutation analysis should be performed on primaries or related metastases. The aim of our study was to evaluate the concordance of K-ras status between primary and related metastases tumors, thus investigate the validity and rigorousness of clinical K-ras testing. Methods: Seventy-six patients with confirmed mCRC treated in Fudan University Shanghai Cancer Center were enrolled. After DNA extraction and PCR amplification, tumor specimens with paired primary tumors and related metastatic sites were put into sequencing analysis. And the K-ras mutation status in exon 2 was assessed. Results: K-ras mutation was detected in 31 out of 76 primary tumours (40.8%) and also 40.8% of the metastatic sites. But discordance was found between primary tumor and metastasis in 15 cases (19.7%): 8 primary tumors had a K-ras mutation with a wildtype metastasis, meanwhile 7 primary tumors were wild type with a K-ras-mutated metastasis. Conclusion: Our study indicated that quite a few mCRC cases have different K-ras status between primary tumors and related metastatic sites, and it’s not very rigorous to choose the anti-EGFR treatments merely according to the primary tumor-K-ras mutation. Further study and consultation are needed on this problem.
Keywords:Colorectal cancer  K-ras gene  Primary tumor  Metastases  Cetuximab  
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