A comparison of ARMS and direct sequencing for EGFR mutation analysis and Tyrosine Kinase Inhibitors treatment prediction in body fluid samples of Non-Small-Cell Lung Cancer patients

Journal of Experimental & Clinical Cancer Research

Xiao-Qing Liu¹  Hong-Jun Gao¹  Bing Liu¹  Cui-Jing Chen¹  Sha Li¹  Hai-Xu Hu¹  Wan-Feng Guo¹  Chuan-Hao Tang¹  Hai-Feng Qin¹  Jian-Jie Li¹  Xiao-Yan Li¹  Bing Liu¹  Yi Liu¹ 

[1] Cancer Center of People's Liberation Army of China, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China

关键词: NSCLC;    TKIs;    ARMS;    Direct Sequencing;    EGFR Mutation;    Body Fluids;   

Others  :  827030
DOI  :  10.1186/1756-9966-30-111

 received in 2011-10-18, accepted in 2011-12-06,  发布年份 2011

【 摘 要 】

Background

Epidermal growth factor receptor (EGFR) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved.

Method

In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The EGFR mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively.

Results

As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma.

Conclusions

When using body fluids for EGFR mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.

【 授权许可】

   
2011 Liu et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

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