Biochemical uncovering of mdm2/p53 complexes in liposarcomas parallels their immunohistochemical detection

Recent observations indicate the existence of pathogenetically distinct gro ups of well-differentiated (WD) dedifferentiated (DD) liposarcomas. In the retroperitoneal WD-DD liposarcomas, the predominant phenotype is represente d by the aberrant (overexpressed) mdm2+/p53+ wild-type profile. At the nonr etroperitoneal site, the WD liposarcomas present a wider association of MDM 2/P53 gene expression; i.e., mdm2+/p53+, mdm2+/p53-, mdm2-/p53+ and mdm2-/p 53-, and TP53 mutations seem to con elate with the dedifferentiation proces s. A biochemical study of mdm2-p53 association in 11 tumor samples characte rized by the presence of different mdm2 and p53 immunophenotypes was perfor med. Immunoprecipitation assays using a p53-specific antibody were performe d on tumor tissue and surrounding normal tissue; the immunoprecipitated mat erial was then investigated for the presence of p53 (control) and of coimmu noprecipitated mdm2. This biochemical analysis showed that, in mdm2+/p53+/w ild-type retroperitoneal liposarcomas, a band corresponded to mdm2 protein in the cellular lysates immunoprecipitated with a p53-directed antibody. In contrast, the mdm2+/p53- liposarcoma did not evidence the presence of mdm2 protein nor was p53 protein available to direct immunoprecipitation, as in the p53 mutant tumor samples with mdm2-/p53+ and mdm2-/p53- phenotypes. Fr om the normal counterpart of retroperitoneal liposarcoma lysates, no p53 pr otein was immunoprecipitated. The findings in this study agree with the mol ecular data and they show the physical association of mdm2 and p53 in fresh Liposarcoma surgical specimens.