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

  • Jingya Zhao
  • Xiaoying Wang
  • Liang Xue
  • Nuo Xu
  • Xin Ye
  • Haiying Zeng
  • Shaohua Lu
  • Jie Huang
  • Sujie Akesu
  • Chen Xu
  • Deming He
  • Yunshan Tan
  • Qunying Hong
  • Qun Wang
  • Guanshan Zhu
  • Yingyong HouEmail author
  • Xin ZhangEmail author
Original Article – Clinical Oncology

Abstract

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 16.0–20.0), which was significantly longer than that in patients with a low score (8.0 months; 95 % CI 2.6–13.4; 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.

Keywords

Activating EGFR mutation EGFR-tyrosine kinase inhibitor Mutation-specific antibody Non-small-cell lung cancer 

Notes

Acknowledgments

We are grateful for the helpful suggestion provided by AstraZeneca Innovation Center China.

Conflict of interest

We have full control of all primary data and agree to allow the journal to review our data if requested. All authors declare that they have no conflicts of interest for this manuscript.

Ethical standard

The Ethical Committee of Shanghai Zhongshan Hospital approved the current research, and all patients gave their informed consent prior to their inclusion in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • 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
    Email author
  • Xin Zhang
    • 1
    Email author
  1. 1.Department of Pulmonary Medicine, Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Department of Pathology, Zhongshan HospitalFudan UniversityShanghaiChina
  3. 3.Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
  4. 4.AstraZeneca Innovation Center ChinaShanghaiChina

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