Monoclonality of atypical adenomatous hyperplasia of the lung

Atypical adenomatous hyperplasia (AAH) of the lung has been postulated as a possible precursor lesion of bronchioloalveolar carcinoma (BAC). The clona lity of AAHs from seven female patients was analyzed to determine whether A AH is a monoclonal expansion, All AAHs were identified in lungs surgically resected for BAG. The clonality of the BAC and bronchiolar metaplasia in ea ch case was also analyzed. Approximately 500 cells in each lesion were prec isely microdissected from methanol-fixed sections. Adjacent normal lung tis sue was collected as a normal control, DNA was extracted for clonal analysi s based on an X-chromosome-linked polymorphic marker, the human androgen re ceptor gene (HUMARA). HUMARA was found to be amplified with or without prev ious digestion by the methylation-sensitive restriction endonuclease NpaII. Five cases were informative, hu 10 AAHs and 7 BACs obtained from the infor mative cases showed monoclonality, whereas the control cells showed polyclo nality. Three different AAH lesions in a single case showed both possible p atterns of monoclonality. BAC and contiguous AAH showed identical monoclona lity in mo cases. Tno lesions of bronchiolar metaplasia, which was consider ed reactive, were polyclonal. Our results demonstrated the monoclonal natur e of AAH, and this finding suggests that AAH is a precursor of BAC or a pre neoplastic condition.