ATYPICAL ALVEOLAR HYPERPLASIA - RELATIONSHIP WITH PULMONARY ADENOCARCINOMA, P53, AND C-ERBB-2 EXPRESSION

Atypical alveolar hyperplasia (AAH) has recently been described in hum an lungs in association with primary lung cancer, particularly adenoca rcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchym al) adenocarcinoma of the lung does not have a well-recognized progeni tor lesion. Epidemiological, morphometric, and cytofluorometric data i n the literature suggest that AAH is a candidate premalignant entity, In this study, 97 AAH lesions were found in lungs resected from 29 pat ients (1-13 lesions per case, mean 3.5) being treated for presumed car cinoma (25/29 had adenocarcinoma). From a study case-load of 285 adeno carcinoma-bearing lungs, the AAH incidence was 8.8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antib odies against Ki67 (MIB1), p53 (DO7), and c-erbB-2 (NCL-CB11). Ki67 wa s expressed in up to 10 per cent of AAH nuclei. Thirty-nine lesions (5 8 per cent) showed stainable p53 protein, while five (7 per cent) expr essed membrane c-erbB-2 oncoprotein. These latter five lesions were al l strongly positive for p53, and both p53 and c-erbB-2 staining was as sociated with increased cellular crowding and pleomorphism in AAH. The se data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premali gnant.