Apoptotic activity is increased in parallel with the metaplasia-dysplasia-carcinoma sequence of the bronchial epithelium

A high level of apoptotic activity and an independence of apoptosis from th e expression of p53 and bcl-2 have been observed in non-small-cell lung car cinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e , mild, moderate and severe dysplasias and carcinoma in situ) bronchial epi thelia to evaluate whether differences in the apoptotic activity could alre ady be seen in the stages preceding squamous cell carcinoma of the lung (SQ CLC). Apoptotic cells and bodies were Visualized by 3' end labelling. The e xpression of p53 and members of the bcl-2 gene family, such as bcl-2, bar a nd mcl-1. were determined immunohistochemically with specific antibodies. T he relative number of apoptotic cells and bodies [apoptotic index (Al%)] wa s already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the Als of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significan tly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apopto sis did not correlate with the expression of p53, bcl-2, bar and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma sequence in the lung, the elevation of the Al% is an early event associated with cell proliferati on activity, but is independent of the expression of p53, bcl-2, mcl-1 and bar.