EXPRESSION OF P21(WAF1 CIP1), MDM2 AND P53 IN-VIVO - ANALYSIS OF CYTOLOGICAL PREPARATIONS/

The aim of this study was to test the hypothesis that expression of p2 1(waf1/Cip1) and MDM2 could be used as indicators of the activity of w ild-type p53 which can transcriptionally activate the p21(waf1/Cip1) a nd mdm2 genes. In cytological preparations of serous fluids, the expre ssion of p53, p21(waf1/Cip1) and MDM2 protein was assessed by immunohi stochemistry. A series of 50 cases was assessed for both p53 and p21(w af1/Cip1) expression and a subset of 37 cases had sufficient material for analysis of MDM2. In samples in which there were reactive mesothel ial cells (n=48) there was general concordance between p53 and p21(waf 1/Cip1) expression, but in nine cases p21(waf1/Cip1) was expressed in the absence of detectable p53. Similarly, MDM2 expression was not corr elated with p53 in 15 of 31 cases. p21(waf1/Cip1) was correlated with MDM2 in 24 of 31 cases, while in the remaining seven, MDM2 was express ed without detectable p21(waf1/Cip1) immunoreactivity. In samples with neoplastic cells (n=18) the presence of p21(waf1/Cip1) and MDM2 expre ssion was always associated with p53 expression. Polymorphonuclear leu cocytes frequently showed p21(waf1/Cip1) immunoreactivity, and this wa s confirmed by immunoblotting of peripheral blood polymorphonuclear le ucocytes. These data indicate that in general p21(waf1/Cip1) expressio n correlates with p53 expression in reactive mesothelial cells, consis tent with a known mechanism of regulation. However, in reactive mesoth elial cells, MDM2 expression is perhaps dissociated from p53 expressio n, contrary to current models of MDM2 regulation. Finally, in addition to many normal tissues, it is likely that in reactive mesothelial cel ls and some tumours p21(waf1/Cip1) expression is not dependent on the presence of wild-type p53 protein. In conclusion, p53 status cannot be reliably predicted based only on p21(waf1/Cip1) or MDM2 expression.