title: Comparison of different methods for detecting epidermal growth factor receptor mutations in peripheral blood and tumor tissue of non-small cell lung cancer as a predictor of response to gefitinib.
abstract: BACKGROUND
  Previous studies have reported that epidermal growth factor receptor (EGFR) mutation in tumor tissue and peripheral blood can predict the response to EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC). However, the heterogeneity of the sample sources makes it difficult to evaluate the detecting methodologies. The goal of this study is to compare different methods for analyzing EGFR mutation in blood and tumor tissue.
  
  
  METHODS
  Fifty-one advanced NSCLC patients treated with gefitinib were included in the study. The EGFR mutation status of each patients' blood was analyzed by denaturing high-performance liquid chromatography (DHPLC), mutant-enriched liquidchip (ME-Liquidchip), and Scorpion Amplification Refractory Mutation System (Scorpion-ARMS) kits. EGFR mutation information in paired tumor samples detected by Scorpion-ARMS served as a reference. Comparative analyses were performed on mutation status results obtained from different methods and on the association between the clinical outcome of TKI treatment and EGFR mutation status.
  
  
  RESULTS
  The response rate (RR) in the whole group was 33.3%. EGFR mutation rates were identified as 15.7%, 27.5%, and 29.4% by DHPLC, ME-Liquidchip, and Scorpion-ARMS in blood, respectively. In 34 cases that had paired tumor samples, the mutation rate in tissue was 41.2%. The RRs of patients with mutation detected by different methods were 71.4% (tumor), 62.5% (blood, DHPLC), 50.0% (blood, ME-Liquidchip), and 66.7% (blood, Scorpion-ARMS). EGFR mutation detected by Scorpion-ARMS in blood and tumor tissues had better prediction of RR to EGFR-TKI (P = 0.002 and P = 0.001) than mutation detected with DHPLC and ME-Liquidchip.
  
  
  CONCLUSIONS
  Tumor tissue sample is the best source for EGFR mutation analysis in NSCLC patients. Peripheral blood samples may be used as an alternative source only in special conditions. Scorpion-ARMS, DHPLC, or ME-Liquidchip methods are all optional for detecting tumor EGFR mutation from blood.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Jingxun
authors.initials: J
authors.lastname: Wu
authors.forename: Cong
authors.initials: C
authors.lastname: Xue
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Liping
authors.initials: L
authors.lastname: Lin
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.forename: Yachao
authors.initials: Y
authors.lastname: Lu
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Jiasen
authors.initials: J
authors.lastname: Xu
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang