P53 PROTEIN EXPRESSION IN NON-HODGKINS-LYMPHOMA - COMPARATIVE-STUDY WITH THE WILD-TYPE P53 INDUCED PROTEINS MDM2 AND P21 WAF1/

Aims-To investigate the pattern of expression of p53 protein and two w ild type p53 induced proteins (mdm2 and p21/waf1) as an indirect way o f assessing p53 gene status in non-Hodgkin's lymphoma. Methods-Formali n fixed, paraffin wax embedded tissue from 87 cases of nodal non-Hodgk in's lymphoma, comprising 52 high grade and 35 low grade tumours, was stained by immunohistochemistry for p53, mdm2 and p21/waf1 proteins. R esults-p53, mdm2 and waf1/p21 proteins were expressed in 36/52, 21/52 and 31/52 high grade and 3/35, 21/35 and 3/35 low grade non-Hodgkin's lymphomas, respectively. Parallel p53/mdm2 protein expression was foun d in 23 cases (21 high grade and two low grade). These 23 cases were a lso positive for p21/waf1 protein expression. Discordant p53 positive/ mdm2 negative protein expression was found in 16 cases (15 high grade and one low grade). Eleven (10 high grade and one low grade) of these 16 cases were p21/waf1 positive and the remaining five high grade non- Hodgkin's lymphomas were p21/waf1 negative. Mdm2 and p21/waf1 proteins were not expressed in the absence of p53 protein expression. Conclusi ons-p53, mdm2 and waf1/p21 protein expression is more frequently assoc iated with aggressive histotypes of non-Hodgkin's lymphoma. Parallel e xpression of p53, mdm2 and p21 proteins may represent non-Hodgkin's ly mphomas with a wild type p53 gene as mdm2 and p21 proteins can be indu ced by the wild type gene. In these cases p53 protein expression may r esult from stabilisation via complex formation with the mdm2 protein. This could be important in the pathogenesis of these cases as mdm2 may deregulate the p53 dependent-growth suppressive pathway. Discordant p 53 positive/mdm2 negative/p21 negative protein expression may represen t non-Hodgkin's lymphoma with p53 gene mutations unable to activate ex pression of mdm2 and p21 proteins. Non-Hodgkin's lymphoma with p53 pos itive/mdm2 negative/p21 positive protein expression may have either wi ld type p53 with deregulated mdm2 gene expression or mutated p53 gene with p53 independent p21 expression.