title: Direct comparison of 3 PCR methods in detecting EGFR mutations in patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutations are predictive of response to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Several methods have been used to detect EGFR mutations; however, it is not clear which is the most suitable for use in the clinic. In this study, we directly compare the clinical sensitivity and specificity of 3 PCR methods.
  
  
  METHODS
  We compared the 3 PCR methods (mutant-enriched PCR, PNA-LNA PCR, and PCR clamp) in patients with advanced NSCLC. A patient who showed sensitive mutations by at least 1 PCR method was treated with gefitinib. A patient who showed no sensitive mutations was treated with chemotherapy with cytotoxic agents.
  
  
  RESULTS
  Fifty patients with advanced NSCLC previously untreated with EGFR-TKIs were enrolled in this trial. Seventeen patients were harboring EGFR mutations, 5 of whom showed discrepancies between the results of different PCR methods. All 5 patients responded to gefitinib. All patients harboring EGFR mutations received gefitinib treatment and 21 of 33 EGFR-mutation-negative patients received chemotherapy with cytotoxic agents. Median progression-free survival of the gefitinib group and the chemotherapy group were 8.2 and 5.9 months, respectively.
  
  
  CONCLUSIONS
  We considered that all the discrepancies might be false negatives because the patients responded to gefitinib. To clarify the reason for the false negatives of each PCR method, and establish the clinical sensitivity and specificity of each PCR method, a large prospective clinical trial is warranted.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Ikeda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Nanae
authors.initials: N
authors.lastname: Tomonaga
authors.forename: Seiji
authors.initials: S
authors.lastname: Doi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Nakatomi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.forename: Kohei
authors.initials: K
authors.lastname: Motoshima
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors