ENHANCED APOPTOSIS PREDICTS SHORTENED SURVIVAL IN NON-SMALL-CELL LUNG-CARCINOMA

This study was undertaken to determine the extent of apoptosis in lung carcinoma and to evaluate it as a prognostic marker. A series of 75 l ung carcinomas (47 squamous cell carcinomas, 24 adenocarcinomas, 3 sma ll cell carcinomas, and 1 large cell carcinoma) was analyzed for the e xtent of apoptosis by using the 3' end-labeling method of DNA in tissu e sections, Apoptosis was correlated with the rate of cell proliferati on, the immunohistochemically detectable p53 and bcl-2, the extent of tumor necrosis, and the survival data. The end-labeling method allowed a precise evaluation of the extent of apoptosis. In tumor tissue, the number of apoptotic bodies was roughly 2-fold greater than the number of apoptotic cells, whereas in nonneoplastic control tissues, the rat io was 1:1. The apoptotic indexes (percentages of apoptotic cells and bodies among tumor cells) were slightly higher in adenocarcinoma than in squamous cell carcinoma. There was no association between the exten t of apoptosis and the expression of proliferating cell nuclear antige n or p53. On the other hand, tumor necrosis correlated significantly w ith proliferating cell nuclear antigen and p53 positivity (P = 0.00025 and 0.00087, respectively). Surprisingly, the extent of apoptosis was also found to be independent of the expression of bcl-2, Patients wit h apoptotic indexes greater than 1.5% had significantly shorter surviv al time than patients with apoptotic indexes equal to 1.50% or less (P < 0.01 by log rank). Aberrant p53 positivity also predicted a poor pr ognosis (P < 0.002 by log rank). By multivariate analysis, enhanced ap optosis showed a 1.9-fold risk (P = 0.04), and p53 positivity showed a 2.3-fold risk (P = 0.005) for a shortened survival. We conclude that both enhanced apoptosis and p53 positivity are independent prognostic markers in non-small cell lung carcinoma, predicting shortened surviva l time of the patients.