PROLIFERATIVE POTENTIAL AND P53 OVEREXPRESSION IN PRECURSOR AND EARLY-STAGE LESIONS OF BRONCHIOLOALVEOLAR LUNG-CARCINOMA

To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BA C), we evaluated the lesion size, growth fraction, and p53 overexpress ion of atypical adenomatous hyperplasia (AAH) and early stage BAC. AAH was classified as showing low grade or high grade atypia. AAH-like ca rcinoma, presumably very early stage BAC, was distinguished from AAH i n that it exhibited remarkable atypia suggestive of malignant potentia l and from overt BAC in that it lacked unequivocal malignant features, including invasive/destructive growth. The growth fraction was determ ined immunohistochemically in terms of the Ki-67 labeling index. The o verexpression of p53 was evaluated by assessing the nuclear accumulati on of immunoreactive p53 protein. Both the lesion size and the growth fraction increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to overt adenocarcinoma. The overexpression of p53 in A AH-like carcinoma was similar to that in overt adenocarcinoma and was more frequent than that in AAH. Our findings indicate that AAH, AAH-li ke carcinoma, and overt BAC represent different categories, although t he cellular events occurring in these lesions presumably represent a c ontinuous spectrum of the changes that are reflected in the cytomorpho logy and lesion size. The findings here suggest that AAH and AAH-like carcinomas constitute a population of heterogeneous lesions representi ng different steps toward overt BAC.