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 the expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e. mild, moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to evaluate whether differences in the apoptotic activity could already be seen in the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells and bodies were visualized by 3' end labelling. The expression of p53 and members of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined immunohistochemically with specific antibodies. The relative number of apoptotic cells and bodies [apoptotic index (AI%)] was already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the AIs of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significantly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apoptosis did not correlate with the expression of p53, bcl-2, bax and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma sequence in the lung, the elevation of the AI% is an early event associated with cell proliferation activity, but is independent of the expression of p53, bcl-2, mcl-1 and bax.