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JMD 2003, Vol. 5, No. 2
Copyright © 2003 American Society for Investigative Pathology & Association for Molecular Pathology

Chromosomal Abnormalities in Non-Small Cell Lung Carcinomas and in Bronchial Epithelia of High-Risk Smokers Detected by Multi-Target Interphase Fluorescence in Situ Hybridization

Maura Santos Romeo^*, Irina A. Sokolova, Larry E. Morrison, Chan Zeng, Anna E. Barón, Fred R. Hirsch^*, York E. Miller^*, Wilbur A. Franklin^¶ and Marileila Varella-Garcia^*

From the Departments of Medicine, * Preventive Medicine and Biometrics, and Pathology, ^¶ School of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; the Department of Medicine, Denver Veterans Administration Medical Center, Denver, Colorado; and Vysis, Inc., Downers Grove, Illinois

Human lung carcinogenesis is accompanied by complex chromosomal changes that may be detected in interphase cells by fluorescence in situ hybridization (FISH) assay using recently developed multitarget DNA probes. Touch preparations of 20 non-small cell lung carcinomas, sputum specimens from 3 patients with lung cancer and from 11 ex-smokers without lung cancer, and cultured benign bronchial epithelium of 42 high-risk smokers, 9 of whom had concurrent invasive carcinoma, were tested using a four-color FISH probe (LAVysion) targeting centromere 6, 5p15.2, 7p12 (EGFR), and 8q24 (MYC). Significantly high frequencies of abnormal cells were found in each of the 20 NSCLC (100%) and in the 3 sputum specimens from lung cancer patients. None of the cytologically normal sputa contained FISH abnormalities. Cultured bronchial epithelial cells from 11 of 42 patients (26%) were abnormal for at least one probe. Abnormal FISH patterns had no association with gender, presence of tumor or histology. Multicolor FISH can readily detect chromosomal abnormalities in imprints and sputa from lung carcinomas. Chromosomal aneusomy is also frequent in bronchial epithelial cells from long-term smokers. The prognostic significance of the multicolor LAVysion FISH probe set should be validated in a controlled clinical trial.

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