title: The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking.
abstract: OBJECTIVE
  To assess the prevalence of EML4-ALK rearrangement gene measured by immunohistochemistry in an unselected population-based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age.
  
  
  RESULTS
  All patients diagnosed in the population of the greater Copenhagen area were included, irrespective of gender, age, smoking habits, stage or type of available diagnostic material. Tumours were stained with immunohistochemistry (clone 5A4). Immunohistochemistry-positive tumours were tested by fluorescence in-situ hybridization (FISH). During a 16-month period, 760 patients in the population were diagnosed with ACL. In 2.6% there was insufficient material for ALK testing (20 of 760). Eleven per cent of the remaining 740 ACL patients were never smokers, 43% were ex-smokers smokers and 46% were current smokers. Fourteen patients [1.9%, 95% confidence interval (CI) = 1.1-3.2] were ALK-positive by immunohistochemistry. Nine of 82 never-smokers (11%, 95% CI = 5.9-19.6) and five of 652 ex- or current smokers (0.8%, 95% CI = 0.4-2.1) were ALK-positive. Only two ALK-positive patients were found among 586 heavy smokers (> 15 pack-years) (0.3%, 95% CI = 0.09-1.2). Thirteen of the 14 immunohistochemistry-positive patients were FISH-positive. All ALK-positive tumours were TTF1-positive. The number needed to test (NNT) to identify one ALK positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.
  
  
  CONCLUSIONS
  Immunohistochemical analysis of ALK rearrangement was possible in 97.4% of patients. ALK rearrangement was found primarily in never smokers. NNT to identify one ALK-positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Birgit G
authors.initials: BG
authors.lastname: Skov
authors.affiliation: Copenhagen Academy for Medical Education and Simulation (CAMES), Rigshospitalet and the Capital Region of Denmark, Copenhagen, Denmark.
authors.forename: Paul
authors.initials: P
authors.lastname: Clementsen
authors.affiliation: Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Larsen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens B
authors.initials: JB
authors.lastname: Sørensen
authors.affiliation: Department of Oncology, Herlev University Hospital, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Mellemgaard
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D014157:Transcription Factors; D044465:White People
chemical_list: D004268:DNA-Binding Proteins; C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; C504003:TTF1 protein, human; D014157:Transcription Factors
keywords: 
  ACL
  ; ALK rearrangement; smoking history; unselected Caucasian population