IMMUNOHISTOCHEMICAL DETECTION OF BCL2, P53, MDM2 AND P2L 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 ol p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 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 defected 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 mdm2, and two were positive for both p53 and mdm2 proteins. The sign ificant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis dur ing neoplastic transformation. The expression of p53 protein in SCLC i s likely to be related to underlying p53 gene mutations since these ge netic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours wit h wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent t umours with p53-independent p21 protein expression. Coexpression of p5 3 and bcl-2 proteins in a proportion of SCLC suggests that in these tu mours p53 does not maintain its suppressive effect on bcl-2 expression as has been reported in vitro. Further studies at the DNA and RNA lev el are required to clarify the involvement of bcl-2, p53, mdm2 and waf 1 genes in SCLC pathogenesis.