Evidence of cumulative gene losses with progression of XXXX of the bronchus.

@entity1 @entity2735 @entity2488 @entity5 @entity1373 @entity1149 @entity189 @entity1491 @entity1544 @entity153 @entity74 @entity6349 @entity1141
@entity1 @entity153 is thought to develop through progressive stages from @entity1491 to @entity1544 , @entity1141 , @entity2735 , and finally invasive @entity5 . In this study, we used tissue microdissection to examine loss of heterozygosity of chromosomes 3p21, 5q21, and 9p21 at each stage of the epithelial progression to invasive @entity5 . Forty-eight premalignant/malignant bronchial sites were biopsied from 13 @entity1 (including 9 subjects without @entity5 ) using fluorescence bronchoscopy. Eighteen sites with moderate/severe @entity1141 in 6 @entity1 were subjected to bronchoscopic and molecular follow-up during a 3-month to 2-year period. Seven separate cases of advanced @entity1149 were also analyzed. From the baseline biopsies, the prevalence of 3p and 9p deletions increased significantly from no deletion in the @entity1373 /metaplasia samples (n = 9) to 37 and 31% of the informative cases, respectively, in the @entity1141 samples (n = 29), to 100 and 83%, respectively, for the @entity189 in situ (n = 6), and 100% in the invasive @entity5 (n = 11). Chromosome 5q deletion was significantly more frequent in invasive @entity5 (70% of the informative cases) as compared to @entity2735 (40%), @entity1141 (33%), and @entity1373 /metaplasia samples (11%). The number of chromosome alterations also increased significantly from the lowest to the highest grade lesions, showing evidence of accumulation of @entity74 from one group to another. The molecular follow-up analysis showed that the same genomic alteration can persist in a given @entity6349 bronchial area for several months or years, and that the persistence or the regression of the @entity74 is well correlated with the evolution of the disease on follow-up. Our results suggest that molecular analysis of bronchial biopsies obtained by fluorescence bronchoscopy may be a very useful means to study the natural history of preinvasive @entity2488 and the outcome of interventions, such as with chemopreventive treatment.
