Correlation between genetic alterations and histopathological subtypes in bronchiolo-alveolar carcinoma and atypical adenomatous hyperplasia of the lung

Bronchiolo-alveolar carcinoma (BAC) is a type of lung adenocarcinoma charac terized by growth along the alveolar wall. It is divided into two subtypes: sclerosing BAC (SBAC), which has central fibrosis, and non-sclerosing BAC (NSBAC), which lacks central fibrosis. We compared the genetic alterations in these two types of BAC with those in atypical adenomatous hyperplasia (A AH). There were 39 cases of SBAC, 19 of NSBAC and 20 of AAH. To detect the loss of heterozygosity (LOH) we used the microsatellite markers D3S1234 and D3S1300 on chromosome 3p, IFNA and D9S144 on 9p, and TP53 on 17p. We also used polymerase chain reaction-SSCP analysis and direct sequencing to exami ne a point mutation of the p53 gene at exons 5-8. At the TP53 locus, the fr equencies of LOH showed a statistical rank-difference correlation among AAH , NSBAC and SBAC. On chromosomes 3p and 9p there were no statistical differ ences of LOH among AAH, NSBAC and SBAC. We detected a significant statistic al rank-difference correlation in the p53 mutation among AAH, NSBAC and SBA C. These findings suggest that a process of multistep carcinogenesis from A AH through NSBAC to SBAC might occur in some cases of adenocarcinoma, and L OH of 3p and 9p might be an early event of carcinogenesis, while the p53 mu tation might be a later event.