Evidence of Cumulative Gene Losses with Progression of Premalignant Epithelial Lesions to Carcinoma of the Bronchus

摘要: Human bronchial carcinoma is thought to develop through progressive stages from basal cell hyperplasia squamous metaplasia, dysplasia, in situ, and finally invasive cancer. In this study, we used tissue microdissection examine loss of heterozygosity chromosomes 3p21, 5q21, 9p21 at each stage the epithelial progression cancers. Forty-eight premalignant/malignant sites were biopsied 13 patients (including 9 subjects without cancer) using fluorescence bronchoscopy. Eighteen with moderate/severe dysplasia 6 subjected bronchoscopic molecular follow-up during a 3-month 2-year period. Seven separate cases advanced non-small cancers also analyzed. From baseline biopsies, prevalence 3p 9p deletions increased significantly no deletion hyperplasia/metaplasia samples (n = 9) 37 31% informative cases, respectively, 29), 100 83%, for carcinomas situ 6), 100% 11). Chromosome 5q was more frequent (70% cases) as compared (40%), dysplasias (33%), (11%). The number chromosome alterations lowest highest grade lesions, showing evidence accumulation genetic damage one group another. analysis showed that same genomic alteration can persist given dysplastic area several months or years, persistence regression abnormality well correlated evolution disease on follow-up. Our results suggest biopsies obtained by bronchoscopy may be very useful means study natural history preinvasive lesions outcome interventions, such chemopreventive treatment.