APOPTOSIS AND EXPRESSION OF BCL-2 PROTEIN ARE INVERSE FACTORS INFLUENCING TUMOR-CELL TURNOVER IN PRIMARY CARCINOID-TUMORS OF THE LUNG

Aims: This study evaluates potential regulating factors in primary pul monary carcinoid tumours, 16 typical and four atypical samples, with s pecial emphasis on apoptosis and the bcl-2 gene family. Furthermore, p 53-related oncogenes were analysed in a search for associated biologic al parameters. Methods and results: The in-situ end-labelling techniqu e (ISEL) was used to determine apoptotic cells, in addition to immunoh istochemical methods, which were used to investigate the expression of the Ki67 antigen (avidinbiotin complex (ABC) method) and bcl-2, bcl-x , p53 p21/wafl, p27 and mdm-2 proteins (catalysed reporter deposition (CARD) technique). The incidence of apoptotic tumour cells was signifi cantly enhanced in typical carcinoids. The bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher p roliferative capacity as well. In contrast, bcl-x was observed predomi nantly in so-called typical carcinoids. The tumour cell turnover index was the most distinguishing parameter between both entities. All carc inoid tumours failed to show a staining for p53, p21/waf, p27 and mdm- 2 proteins. Conclusions: The different biological behaviour of the car cinoid tumours under study seems to be influenced by the bcl-2 gene fa mily preventing programmed cell death. We speculate that this results in a more aggressive course in atypical carcinoid tumours.