The use of mutation-specific antibodies in predicting the effect of EGFR-TKIs in patients with non-small-cell lung cancer

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• 作者：Jingya Zhao (1)
  Xiaoying Wang (1)
  Liang Xue (3)
  Nuo Xu (1)
  Xin Ye (4)
  Haiying Zeng (2)
  Shaohua Lu (2)
  Jie Huang (2)
  Sujie Akesu (2)
  Chen Xu (2)
  Deming He (2)
  Yunshan Tan (2)
  Qunying Hong (1)
  Qun Wang (3)
  Guanshan Zhu (4)
  Yingyong Hou (2)
  Xin Zhang (1)
  
• 关键词：Activating EGFR mutation ; EGFR ; tyrosine kinase inhibitor ; Mutation ; specific antibody ; Non ; small ; cell lung cancer
• 刊名：Journal of Cancer Research and Clinical Oncology
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：140
• 期：5
• 页码：849-857
• 全文大小：855 KB
• 参考文献：1. Azuma K, Okamoto I, Kawahara A et al (2012) Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment. J Thorac Oncol 7(1):122-27 CrossRef
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  4. Inoue A, Suzuki T, Fukuhara T et al (2006) Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 24(21):3340-346 CrossRef
  5. Kato Y, Peled N, Wynes MW et al (2010) Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations. J Thorac Oncol 5(10):1551-558 CrossRef
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  17. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205-16 CrossRef
  18. Tiseo M, Rossi G, Capelletti M et al (2010) Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): study of a comprehensive panel of molecular markers. Lung Cancer 67(3):355-60 lungcan.2009.04.021" target="_blank" title="It opens in new window">CrossRef
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• 作者单位：Jingya Zhao (1)
  Xiaoying Wang (1)
  Liang Xue (3)
  Nuo Xu (1)
  Xin Ye (4)
  Haiying Zeng (2)
  Shaohua Lu (2)
  Jie Huang (2)
  Sujie Akesu (2)
  Chen Xu (2)
  Deming He (2)
  Yunshan Tan (2)
  Qunying Hong (1)
  Qun Wang (3)
  Guanshan Zhu (4)
  Yingyong Hou (2)
  Xin Zhang (1)
  
  1. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, No.180 Fenglin Rd, Shanghai, 200032, China
  3. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No.180 Fenglin Rd, Shanghai, 200032, China
  4. AstraZeneca Innovation Center China, Building 7, No.898 Halei Rd, Zhangjiang Hi-Tech Park, Shanghai, 201203, China
  2. Department of Pathology, Zhongshan Hospital, Fudan University, No.180 Fenglin Rd, Shanghai, 200032, China
  
• ISSN：1432-1335

文摘

Purpose We aimed to quantify the epidermal growth factor receptor (EGFR) mutation in tumors and to analyze its prediction of EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients. Methods We examined EGFR mutation status in 124 lung cancer samples by direct sequencing and amplification refractory mutation system. Among them, 41 were appropriate to quantify the expression of mutant EGFR proteins using immunohistochemistry (IHC) with mutation-specific antibodies. The quantification was determined by both the staining intensity and the proportion of stained tumor cells. Results The median progression-free survival (PFS) in patients with a high score for mutant EGFR expression was 18.0?months (95?% CI 16.0-0.0), which was significantly longer than that in patients with a low score (8.0?months; 95?% CI 2.6-3.4; P?=?0.048). Such significant association with patients-PFS was also apparent in the proportion of stained tumor cells (median, 19.0 vs. 8.0?months; P?=?0.019), but not in the staining intensity (P?=?0.787). Among the 41 specimens, 32 were detected EGFR mutation positive by both direct sequencing and ARMS, referring to a relatively high abundance of mutation, and 26 (81.3?%) of them gained a high expression score of mutant proteins as well. Six samples with mutation negative by direct sequencing but positive by ARMS, which showed a low abundance, and 5 (83.3?%) of them also revealed a low expression score. The EGFR mutation quantitative analysis using mutation-specific IHC was moderately consistent with that by molecular-based assays (P?=?0.001, kappa value 0.50). Conclusions Our results suggest that immunohistochemical analysis with mutation-specific antibodies is a promising approach for quantifying EGFR mutations, and may predict the effect of EGFR-TKI treatment for EGFR mutation-positive NSCLC.