GENESIS OF SQUAMOUS-CELL LUNG-CARCINOMA - SEQUENTIAL-CHANGES OF PROLIFERATION, DNA-PLOIDY AND P53 EXPRESSION

Squamous cell lung carcinomas (SCCs) represent a highly malignant grou p of tumors, and effective treatment is greatly dependent upon early d iagnosis. However, objective diagnosis of atypia is difficult and usef ul markers need to be defined In this study, genomic instability, cell proliferation, and cellular accumulation of mutant p53, as reflected by DNA aneuploidy, proliferating cell nuclear antigen, and p53 immunor eactivity, respectively, were evaluated in bronchial squamous metaplas ia without atypia (n = 4), bronchial squamous metaplasia with low-grad e atypia (n = 12), bronchial squamous metaplasia with high-grade atypi a (n = 15), early-stage SCC (n = 15), and advanced-stage SCC (n = 33). Our results suggest that hyperproliferation is an early even followed by DNA aneuploidy, which in turn precedes p53 immunoreactivity ill th e genesis of SCC. We conclude that routine assessment of proliferating cell nuclear antigen, DNA ploidy, and p53 may be valuable for the ear ly diagnosis of SCC.