title: An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests.
  
  
  METHODS
  DNA admixtures (n = 34; 1%-50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave, and Scorpion Amplification Refractory Mutation System (ARMS). Analysis success, mutation status, and concordance rates were assessed.
  
  
  RESULTS
  All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%-100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%-100% (FFPE; kappa coefficients: 0.88-1.00), 93.1%-100% (BB cytology; 0.86-1.00), and 85.0%-100% (PE cytology; 0.70-1.00), and 93.1%-96.6% (0.86-0.93) between BB cytology and matched FFPE.
  
  
  CONCLUSIONS
  All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations.
authors: Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba. Electronic address: kgoto@east.ncc.go.jp.
authors: K
authors: K
authors: Goto
authors: Department of Thoracic Oncology, Hyogo Cancer Center, Hyogo.
authors: M
authors: M
authors: Satouchi
authors: Pathology Division, Innovative Medical Research Center, National Cancer Center Hospital East, Chiba.
authors: G
authors: G
authors: Ishii
authors: Department of Genome Biology, Kinki University School of Medicine, Osaka.
authors: K
authors: K
authors: Nishio
authors: Department of Respiratory Medicine, Saitama Medical University, Saitama.
authors: K
authors: K
authors: Hagiwara
authors: Department of Thoracic Surgery, Aichi Cancer Center Hospital, Aichi, Japan.
authors: T
authors: T
authors: Mitsudomi
authors: Department of Personalised Healthcare and Biomarkers, AstraZeneca Pharmaceuticals, Macclesfield, UK.
authors: J
authors: J
authors: Whiteley
authors: Department of Personalised Healthcare and Biomarkers, AstraZeneca Pharmaceuticals, Macclesfield, UK.
authors: E
authors: E
authors: Donald
authors: Department of Personalised Healthcare and Biomarkers, AstraZeneca Pharmaceuticals, Macclesfield, UK.
authors: R
authors: R
authors: McCormack
authors: Department of Research and Development, AstraZeneca KK, Osaka, Japan.
authors: T
authors: T
authors: Todo
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors