Expression of p21waf1/Cip1, MDM2 and p53 in vivo: analysis of cytological preparations.
The aim of this study was to test the hypothesis that expression of p21waf1/Cip1 and MDM2 could be used as indicators of the activity of wild-type p53 which can transcriptionally activate the p21waf1/Cip1 and mdm2 genes. In cytological preparations of serous fluids, the expression of p53, p21waf1/Cip1 and MDM2 protein was assessed by immunohistochemistry. A series of 50 cases was assessed for both p53 and p21waf1/Cip1 expression and a subset of 37 cases had sufficient material for analysis of MDM2. In samples in which there were reactive mesothelial cells (n = 48) there was general concordance between p53 and p21waf1/Cip1 expression, but in nine cases p21waf1/Cip1 was expressed in the absence of detectable p53. Similarly, MDM2 expression was not correlated with p53 in 15 of 31 cases. p21waf1/Cip1 was correlated with MDM2 in 24 of 31 cases, while in the remaining seven, MDM2 was expressed without detectable p21waf1/Cip1 immunoreactivity. In samples with neoplastic cells (n = 18) the presence of p21waf1/Cip1 and MDM2 expression was always associated with p53 expression. Polymorphonuclear leucocytes frequently showed p21waf1/Cip1 immunoreactivity, and this was confirmed by immunoblotting of peripheral blood polymorphonuclear leucocytes. These data indicate that in general p21waf1/Cip1 expression correlates with p53 expression in reactive mesothelial cells, consistent with a known mechanism of regulation. However, in reactive mesothelial cells, MDM2 expression is perhaps dissociated from p53 expression, contrary to current models of MDM2 regulation. Finally, in addition to many normal tissues, it is likely that in reactive mesothelial cells and some tumours p21waf1/Cip1 expression is not dependent on the presence of wild-type p53 protein. In conclusion, p53 status cannot be reliably predicted based only on p21waf1/Cip1 or MDM2 expression.
Department of Molecular and Cellular Pathology, University of Dundee, Edinburgh, UK.
S P
SP
Dowell
E
E
McGoogan
S M
SM
Picksley
W S
WS
el-Deiry
B
B
Vogelstein
P A
PA
Hall
D015415:Biomarkers / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis* / Q000096:biosynthesis*; D003581:Cytodiagnosis / Q000379:methods; D003584:Cytological Techniques; D004791:Enzyme Inhibitors / Q000032:analysis; D005122:Exudates and Transudates; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis; D009504:Neutrophils / Q000378:metabolism; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000096:biosynthesis*
D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2