Published ahead of print on June 28, 2007, doi:10.1164/rccm.200609-1329OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200609-1329OC
Spectral Karyotyping Detects Chromosome Damage in Bronchial Cells of Smokers and Patients with Cancer1 Departments of Medicine and 2 Pathology, School of Medicine, University of Colorado, Denver Health Sciences Center, Denver, Colorado; 3 Health One Presbyterian, St. Luke's Hospital, Denver, Colorado; 4 Department of Medicine, Veterans Administration Medical Center, Denver, Colorado; and 5 Department of Surgery, School of Medicine, University of Colorado, Denver Health Sciences Center, Denver, Colorado Correspondence and requests for reprints should be addressed to Wilbur A. Franklin, M.D., University of Colorado, Health Sciences Center at Fitzsimons Department of Pathology, Mail Stop F8102, P.O. Box 6511, Aurora, CO 80045. E-mail: wilbur.franklin{at}uchsc.edu Rationale: Lung cancer is a multistep process that is preceded and often accompanied by molecular cytogenetic lesions in benign bronchial epithelium, the precise character, extent and timing of which are not well defined. Objectives: In this study we comprehensively defined molecular cytogenetic changes in bronchial cells that may precede lung carcinoma using spectral karyotyping (SKY). Methods: SKY was applied to cultured benign bronchial cells from 43 high-risk smokers without carcinoma, 14 patients with concurrent lung carcinoma, and 14 never-smoker healthy volunteers. Measurements and Main Results: The proportion of cells displaying numeric or structural anomalies/total number of metaphase cells was calculated for each case and was referred to as the chromosomal abnormality index. Mean chromosomal abnormality indices were 15.8, 10.1, and 0.7% for patients with cancer, high-risk smokers, and never-smokers, respectively. Clonal abnormalities were found in 17 (40%) of the high-risk smokers without carcinoma and 7 (50%) of the patients with carcinoma, but in none of 14 (0%) never-smokers. Chromosomal gains observed by SKY were confirmed in interphase cultured cells or paraffin sections of biopsy specimens by fluorescence in situ hybridization in 11 of 13 cases for which appropriate probes were available. In 6 of 57 high-risk patients or those with carcinoma, identical clonal abnormalities were dispersed at multiple bronchial sites and were admixed with nonclonal cells. Conclusions: Clonal and single-cell chromosomal abnormalities are frequent in benign bronchial epithelium during lung carcinogenesis, indicating that chromosomal missegregation and other chromosomal rearrangements occur before overt malignancy.
Key Words: FISH • lung cancer • premalignant conditions • spectral karyotype
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