title: Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer.
abstract: Lung cancer specimens display recurrent copy number aberrations in distinguished chromosomal regions as compared with normal lung cells. Such alterations have been utilized in design of fluorescence in situ hybridization (FISH) probe sets in attempts to improve the cytological diagnosis of lung cancer. One of such probe sets, LAVysion, detects copy number changes in the centromeric region of chromosome 6 (CEP6), and regions 5p15, 8q24, and 7p12, often gained in lung cancer.
  
  
  METHODS
  We evaluated the feasibility of the LAVysion multi-color probe set in detection of individuals at high risk of lung cancer by applying the FISH probe set on smears prepared of induced sputa obtained from 20 lung cancer patients, 43 asbestos-exposed workers, 21 heavy tobacco smokers, and 15 healthy never-smokers. The hybridized sputum smears were examined using fluorescence microscopy and the number of signals in epithelial cells was examined throughout the hybridized area. Additionally, we review here the previous studies using LAVysion probe set.
  
  
  RESULTS
  The FISH probe set was slightly more sensitive than cytology alone in detecting lung cancer. No significant differences in copy number gain were found between high-risk individuals and healthy never-smokers. The proportions of individuals with copy number gains in sputa among the lung cancer patients, asbestos-exposed workers, tobacco smokers, and never-smokers were 50, 20, 12, and 27%, respectively, when three or more cells with a copy number gain detected by at least two different probes was used as the cut-off point. In comparison, the sensitivity of cytology in detecting lung cancer was 44%. In the lung cancer patients the number of abnormal cells by FISH correlated well with the cytologic atypia class (Spearman rank correlation coefficient 0.77, p<0.01). Using multivariant variance analysis, gains in CEP6, 5p15, 8q24 and 7p12 were not associated with smoking or asbestos exposure.
  
  
  CONCLUSIONS
  FISH did not significantly exceed the sensitivity of sputum cytology in finding lung cancers. Significant differences were not found between sputa of asbestos-exposed individuals, heavy-smokers and never-smokers. More sensitive methods are needed for the follow-up of populations at high risk of contracting lung cancer.
authors.affiliation: Finnish Institute of Occupational Health, Centre of Expertise for Health and Work Ability, Topeliuksenkatu 41 a A, FI-00250 Helsinki, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Kettunen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Salmenkivi
authors.forename: Katri
authors.initials: K
authors.lastname: Vuopala
authors.forename: Tuula
authors.initials: T
authors.lastname: Toljamo
authors.forename: Eeva
authors.initials: E
authors.lastname: Kuosma
authors.forename: Hannu
authors.initials: H
authors.lastname: Norppa
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.forename: Simo
authors.initials: S
authors.lastname: Kaleva
authors.forename: Matti S
authors.initials: MS
authors.lastname: Huuskonen
authors.forename: Sisko
authors.initials: S
authors.lastname: Anttila
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D001194:Asbestos / Q000633:toxicity; D001980:Bronchi; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012306:Risk; D012680:Sensitivity and Specificity; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000166:cytology*
chemical_list: D001194:Asbestos