title: Impact of EGFR mutation detection methods on the efficacy of erlotinib in patients with advanced EGFR-wild type lung adenocarcinoma.
abstract: BACKGROUND
  Methods used for epidermal growth factor receptor (EGFR) mutation testing vary widely. The impact of detection methods on the rates of response to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-wild type (wt) lung adenocarcinoma patients is unknown.
  
  
  METHODS
  We recruited the Group-I patients to evaluate the efficacy of erlotinib in patients with EGFR-wt lung adenocarcinoma by either direct sequencing (DS) or mutant type-specific sensitive (MtS) methods in six medical centers in Taiwan. Cross recheck of EGFR mutations was performed in patients who achieved objective response to erlotinib and had adequate specimens. The independent Group-II lung adenocarcinoma patients whose EGFR mutation status determined by DS were recruited to evaluate the potential limitations of three MtS methods.
  
  
  RESULTS
  In Group-I analysis, 38 of 261 EGFR-wt patients (14.6%) achieved partial response to erlotinib treatment. Nineteen patients (50.0%) had adequate specimens for cross recheck of EGFR mutations and 10 of them (52.6%) had changes in EGFR mutation status, 5 in 10 by DS and 5 in 9 by MtS methods originally. In Group-II analysis, 598 of 996 lung adenocarcinoma patients (60.0%) had detectable EGFR mutations. The accuracy rates of the three MtS methods, MALDI-TOF MS, Scorpions ARMS and Cobas, were 87.8%, 86.8% and 85.8%, respectively.
  
  
  CONCLUSIONS
  A significant portion of the erlotinib responses in EGFR-wt lung adenocarcinoma patients were related to the limitations of detection methods, not only DS but also MtS methods with similar percentages. Prospective studies are needed to define the proper strategy for EGFR mutation testing.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jeng-Sen
authors.initials: JS
authors.lastname: Tseng
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Liang
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Molecular Biology, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Tsai
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Kun-Chieh
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hsu
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Meen-Hsin
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors