AIMS: This study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl-2 gene family. Furthermore, p53-related oncogenes were analysed in a search for associated biological parameters. METHODS AND RESULTS: The in-situ end-labelling technique (ISEL) was used to determine apoptotic cells, in addition to immunohistochemical methods, which were used to investigate the expression of the Ki67 antigen (avidinbiotin complex (ABC) method) and bcl-2, bcl-x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (CARD) technique). The incidence of apoptotic tumour cells was significantly enhanced in typical carcinoids. The bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher proliferative capacity as well. In contrast, bcl-x was observed predominantly in so-called typical carcinoids. The tumour cell turnover index was the most distinguishing parameter between both entities. All carcinoid tumours failed to show a staining for p53, p21/waf. p27 and mdm-2 proteins. CONCLUSIONS: The different biological behaviour of the carcinoid tumours under study seems to be influenced by the bcl-2 gene family preventing programmed cell death. We speculate that this results in a more aggressive course in atypical carcinoid tumours.
AIMS: This study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl-2 gene family. Furthermore, p53-related oncogenes were analysed in a search for associated biological parameters. METHODS AND RESULTS: The in-situ end-labelling technique (ISEL) was used to determine apoptotic cells, in addition to immunohistochemical methods, which were used to investigate the expression of the Ki67 antigen (avidinbiotin complex (ABC) method) and bcl-2, bcl-x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (CARD) technique). The incidence of apoptotic tumour cells was significantly enhanced in typical carcinoids. The bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher proliferative capacity as well. In contrast, bcl-x was observed predominantly in so-called typical carcinoids. The tumour cell turnover index was the most distinguishing parameter between both entities. All carcinoid tumours failed to show a staining for p53, p21/waf. p27 and mdm-2 proteins. CONCLUSIONS: The different biological behaviour of the carcinoid tumours under study seems to be influenced by the bcl-2 gene family preventing programmed cell death. We speculate that this results in a more aggressive course in atypical carcinoid tumours.
Authors: Dorian R A Swarts; Sandra M H Claessen; Yvonne M H Jonkers; Robert-Jan van Suylen; Anne-Marie C Dingemans; Wouter W de Herder; Ronald R de Krijger; Egbert F Smit; Frederik B J M Thunnissen; Cornelis A Seldenrijk; Aryan Vink; Aurel Perren; Frans C S Ramaekers; Ernst-Jan M Speel Journal: Am J Pathol Date: 2011-07-16 Impact factor: 4.307