title: Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation is the key predictor of EGFR tyrosine kinase inhibitors (TKIs) efficacy in non-small cell lung cancer (NSCLC). We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations.
  
  
  METHODS
  A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system (ARMS). We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate (ORR), disease control rate (DCR) and progression free survival (PFS).
  
  
  RESULTS
  Of all patients, EGFR mutation rate was 28.6% (60/210) by direct sequencing and 45.2% (95/210) by ARMS (P<0.001) respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR (48.0% vs. 80.9%, P=0.004) and shorter median PFS (7.4 vs. 10.5 months, P=0.009) as compared with that of EGFR mutation positive patients by both detection methods.
  
  
  CONCLUSIONS
  Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Zijin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Bie
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Nie
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ai
authors.affiliation: 1 Department of Oncology, 2 Department of Pathology, Beijing Hospital, Beijing 100730, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
keywords: Non-small cell lung cancer (NSCLC); amplification refractory mutation system (ARMS); cytological specimen; epidermal growth factor receptor (EGFR) mutation; gefitinib