title: Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) mutations, especially deletional mutations in exon 19 (DEL) and L858R, predict gefitinib sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we validated EGFR mutation detection using high-resolution melting analysis (HRMA) and evaluated the associations between EGFR mutations and clinical outcomes in advanced NSCLC patients treated with gefitinib on a larger scale.
  
  
  METHODS
  The presence of DEL or L858R was evaluated using HRMA and paraffin-embedded tissues and/or cytologic slides from 212 patients. In 66 patients, the results were compared with direct sequencing data.
  
  
  RESULTS
  HRMA using formalin-fixed tissues had a 92% sensitivity and a 100% specificity. The analysis was successfully completed in 207 patients, and DEL or L858R mutations were detected in 85 (41%) patients. The response rate (78% versus 8%), time-to-progression (median, 9.2 versus 1.6 months), and overall survival (median, 21.7 versus 8.7 months) were significantly better in patients with EGFR mutations (P < 0.001). Even among the 34 patients with stable diseases, the time-to-progression was significantly longer in patients with EGFR mutations. Patients with DEL (n = 49) tended to have better outcomes than those with L858R (n = 36); the response rates were 86% and 67%, respectively (P = 0.037), and the median time-to-progression was 10.5 and 7.4 months, respectively (P = 0.11).
  
  
  CONCLUSIONS
  HRMA is a precise method for detecting DEL and L858R mutations and is useful for predicting clinical outcomes in patients with advanced NSCLC treated with gefitinib.
authors: Division of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
authors: Toshimi
authors: T
authors: Takano
authors: Yuichiro
authors: Y
authors: Ohe
authors: Koji
authors: K
authors: Tsuta
authors: Tomoya
authors: T
authors: Fukui
authors: Hiromi
authors: H
authors: Sakamoto
authors: Teruhiko
authors: T
authors: Yoshida
authors: Ukihide
authors: U
authors: Tateishi
authors: Hiroshi
authors: H
authors: Nokihara
authors: Noboru
authors: N
authors: Yamamoto
authors: Ikuo
authors: I
authors: Sekine
authors: Hideo
authors: H
authors: Kunitoh
authors: Yoshihiro
authors: Y
authors: Matsuno
authors: Koh
authors: K
authors: Furuta
authors: Tomohide
authors: T
authors: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004252:DNA Mutational Analysis / Q000379:methods*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007930:Leucine / Q000737:chemistry / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D001120:Arginine; D066246:ErbB Receptors; D007930:Leucine; D000077156:Gefitinib