EXPRESSION OF BCL-2 IN LUNG NEUROENDOCRINE TUMORS - COMPARISON WITH P53

Several genetic aberrations have been implicated in the carcinogenesis of small cell lung carcinomas (SCLCs), including tumour suppressor ge ne p53 deletion and mutation and amplification of the myc family proto -oncogenes. However, their exact ontogeny and carcinogenesis remain un known. There are no proven aetiological factors for lung carcinoid tum ours. Recent evidence suggests that the genetic regulation of apoptosi s is of critical importance during tumourigenesis and that oncogene an d tumour suppressor genes can regulate the rate, or susceptibility, of cells to undergo apoptosis. In this study, the expression of Bcl-2 pr otein has been investigated in 77 primary lung neuroendocrine tumours, including 55 SCLCs and 22 carcinoid tumours, and compared with p53 ex pression. Of the 77 tumours studied, Bcl-2 immunoreactivity was presen t in 80 per cent of SCLCs, 43 per cent of typical, and 67 per cent of atypical carcinoid tumours with more than 10 per cent tumour cell posi tivity. Western and Northern blot analysis revealed that carcinoid tum ours expressed the 26 kD protein and Bcl-2 transcripts. Whereas 42 per cent of the SCLCs studied displayed p53 protein immunoreactivity in m ore than 10 per cent of tumour cells, p53 positivity was not found in lung carcinoid tumours. There are statistical differences in Bcl-2 and p53 expression between SCLCs and lung carcinoid tumours. These result s suggest that disregulation of the genetic mechanisms controlling apo ptosis is a critical step in the progression of SCLC, and that the exp ression of bcl-2 is involved in the pathogenesis of SCLC and lung carc inoid tumours. The genetic complementation of simultaneously deregulat ed Bcl-2 and p53 may be implicated in the multistep tumourigenesis of small cell lung cancer. (C) 1998 John Wiley & Sons, Ltd.