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EGFR Fluorescence In situ Hybridization Pattern of Chromosome 7 Disomy Predicts Resistance to Cetuximab in KRAS Wild-type Metastatic Colorectal Cancer Patients
Li, Yu-Hong2,3; Wang, Fang1; Shen, Lin4; Deng, Yan-Ming5; Shao, Qiong1; Feng, Fen3; An, Xin3; Wang, Feng-Hua3; Wang, Zhi-Qiang3; Xu, Rui-Hua2,3; Shao, Jian-Yong1,2
刊名CLINICAL CANCER RESEARCH
2011-01-15
DOI10.1158/1078-0432.CCR-10-0208
17期:2页:382-390
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者Beijing Merck Pharmaceutical Consulting Let ; Beijing Merck Pharmaceutical Consulting Ltd ; Ministry of Science and Technology of P.R. China ; Ministry of Education of P. R. China ; Beijing Merck Pharmaceutical Consulting Let ; Beijing Merck Pharmaceutical Consulting Ltd ; Ministry of Science and Technology of P.R. China ; Ministry of Education of P. R. China
研究领域[WOS]Oncology
关键词[WOS]GENE COPY NUMBER ; FACTOR RECEPTOR GENE ; PLUS IRINOTECAN ; MUTATION STATUS ; CHEMOTHERAPY ; OXALIPLATIN ; FISH
英文摘要

Purpose: Metastatic colorectal cancer patients with low epidermal growth factor receptor (EGFR) gene copy number are unlikely to respond to anti-EGFR monoclonal antibody (mAb) treatment. The objective of this study was to investigate EGFR fluorescence in situ hybridization (FISH) patterns of chromosome 7 disomy with efficacy of cetuximab therapy in metastatic colorectal cancer patients.

Experimental Design: We detected the EGFR FISH patterns and KRAS status in 74 tumors from cetuximab-treated metastatic colorectal cancer patients and analyzed with response rate (RR) and progression-free survival (PFS).

Results: One of the 16 (6.25%) patients with chromosome 7 homogeneous disomy (defined as FISH negative) had objective response to cetuximab. A total of 53(76.8%) patients with chromosome 7 pattern of variable ratios of disomy versus polysomy (defined as FISH positive) had a significantly higher RR (37.7% versus 6.25%; P = 0.01), a trend towards longer PFS (4.5 versus 2.9 months; P = 0.07). Among 54 KRAS wild-type patients, EGFR FISH-positive patients had significantly higher RR (51.3% versus 9%; P = 0.01) and longer PFS (5.0 versus 2.3 months; P = 0.02) than EGFR FISH-negative patients. However, among 20 KRAS mutant-type patients, there was no difference in RR (0% versus 0%) and PFS (2.5 versus 3.8 months; P = 0.51) between EGFR FISH-positive and -negative patients.

Conclusion: Our results show firstly that patients with EGFR FISH pattern of chromosome 7 disomy have a very low chance to benefit from cetuximab-based therapy. EGFR FISH pattern of chromosome 7 disomy may be as a negative predicative factor for cetuximab response in KRAS wild-type metastatic colorectal cancer patients. Clin Cancer Res; 17(2); 382-90. (C)2011 AACR.

语种英语
资助者Beijing Merck Pharmaceutical Consulting Let ; Beijing Merck Pharmaceutical Consulting Ltd ; Ministry of Science and Technology of P.R. China ; Ministry of Education of P. R. China ; Beijing Merck Pharmaceutical Consulting Let ; Beijing Merck Pharmaceutical Consulting Ltd ; Ministry of Science and Technology of P.R. China ; Ministry of Education of P. R. China
WOS记录号WOS:000286221700022
引用统计
被引频次:21[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66344
专题北京大学临床肿瘤学院_胃肠肿瘤中心
作者单位1.Sun Yat Sen Univ, Ctr Canc, Dept Pathol, Guangzhou 510060, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol So China, Guangzhou 510060, Guangdong, Peoples R China
3.Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510060, Guangdong, Peoples R China
4.Beijing Canc Hosp, Dept Gastrointestinal Oncol, Beijing, Peoples R China
5.First Peoples Hosp Foshan, Ctr Canc, Dept Med Oncol, Foshan, Guangdong, Peoples R China
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Li, Yu-Hong,Wang, Fang,Shen, Lin,et al. EGFR Fluorescence In situ Hybridization Pattern of Chromosome 7 Disomy Predicts Resistance to Cetuximab in KRAS Wild-type Metastatic Colorectal Cancer Patients[J]. CLINICAL CANCER RESEARCH,2011,17(2):382-390.
APA Li, Yu-Hong.,Wang, Fang.,Shen, Lin.,Deng, Yan-Ming.,Shao, Qiong.,...&Shao, Jian-Yong.(2011).EGFR Fluorescence In situ Hybridization Pattern of Chromosome 7 Disomy Predicts Resistance to Cetuximab in KRAS Wild-type Metastatic Colorectal Cancer Patients.CLINICAL CANCER RESEARCH,17(2),382-390.
MLA Li, Yu-Hong,et al."EGFR Fluorescence In situ Hybridization Pattern of Chromosome 7 Disomy Predicts Resistance to Cetuximab in KRAS Wild-type Metastatic Colorectal Cancer Patients".CLINICAL CANCER RESEARCH 17.2(2011):382-390.
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