title: Detection of ALK fusion in lung cancer using fluorescence in situ hybridization.
abstract: OBJECTIVE
  To develop an easy-to-use technique for EML4-ALK detection and establish the effective selection of candidates for screening.
  
  
  BACKGROUND
  We previously reported clinicopathological findings of patients with lung cancer harboring the EML4-ALK fusion gene. Anaplastic lymphoma kinase inhibitors have therapeutic effects in lung cancer patients with EML4-ALK, accounting for merely 1%-5% of lung cancers.
  
  
  METHODS
  We investigated EML4-ALK in tumors from 581 patients. EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. To establish an algorithm to restrict candidates chosen for ALK fusion gene detection, clinicopathological findings as well as EGFR, ERBB2, and KRAS mutations were analyzed.
  
  
  RESULTS
  8 (1.3%) tumors had EML4-ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. We screened 581 patients with tumors and another 27 who were nonsmokers or mild smokers (<20 packs per year) lacking EGFR, KRAS, and ERBB2 mutations and who had adenocarcinomas exhibiting an acinar component with moderate or poor differentiation. Of the 27 patients, 8 (29.6%) had EML4-ALK.
  
  
  CONCLUSIONS
  We propose criteria for selecting candidates for efficient detection of the fusion gene.
authors.affiliation: Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, and Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. masa0425@kuhp.kyoto-u.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kikuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis*; D055815:Young Adult
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion