ATYPICAL ADENOMATOUS HYPERPLASIA AND BRONCHOALVEOLAR LUNG-CARCINOMA -ANALYSIS BY MORPHOMETRY AND THE EXPRESSIONS OF P53 AND CARCINOEMBRYONIC ANTIGEN

Atypical adenomatous hyperplasia (AAH) of the lung is a putative precu rsor of bronchoalveolar carcinoma (BAC). To define the steps in its de velopment and to clarify at which stage critical cellular events occur , we studied 65 lesions of AAH, early BAG, and overt BAC by morphometr ic analysis and immunohistochemical evaluation of expression of p53 pr otein and carcinoembryonic antigen (CEA). Both the nuclear area and le sion size increased from AAH to early BAC and to overt BAG; the standa rdized variation of nuclear area was smallest in overt BAG. Discrimina nt analysis using these morphometric parameters revealed high accuracy rates for the respective categories. Analysis of distribution of lung lesions in terms of nuclear area and lesion size yielded effective, p otentially diagnostic cutoff values for distinction between AAH and ea rly BAG. Both p53 and CEA expression tended to increase with the advan ce of atypia grade. In particular, high-level p53 expression was stron gly correlated with overt BAG. These findings indicate that our classi fication of lung lesions is reproducible and thus useful for analyzing the development of BAG. Furthermore, some kinds of p53 gene abnormali ties that are correlated with high-level p53 expression likely play an important role in the progression of early to overt BAC.