IMMUNOHISTOCHEMICAL DETECTION OF BCL2, P53, MDM2 AND P21 WAF1 PROTEINS IN SMALL-CELL LUNG CARCINOMAS/

Thirty-one cases of small cell lung carcinomas (SCLC) were investigate d by immunohistochemistry for the expression of bcl-2, p53 and the wil d-type (wt) p53-induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (4 2%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/32 cases (45%) were only bcl-2 positive, 3/31 (11%) wer e only p53 positive, 10/31 (32%) were positive for both proteins and 4 /31 (13%) were negative for both proteins. Mdm2 protein was detected i n 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 an d mdm5 and two were positive for both p53 and mdm2 proteins. The signi ficant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis duri ng neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these gen etic alterations are very frequent in SCLC. This can be supported by o ur findings that 11/113 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53(+)/mdm2(+)/p21(+) phenotype may represent tumou rs with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53/mdm2-/p21(+) phenotype may repr esent tumours with p53-independent p21 protein expression. Coexpressio n of p53 and bcl-2 protein in a proportion of SCLC suggests that in th ese tumours p53 doses not maintain its suppressive effect on bcl-2 exp ression as it has been reported in vitro. Further studies at DNA and R NA let el are required to clarify the involvement of bcl-5 p53, mdm2 a nd waf1 genes in SCLC pathogenesis.