Immunoreactivity of p53, mdm2, and p21(WAF1) in dedifferentiated liposarcoma: Special emphasis on the distinct immunophenotype of the well-differentiated component

Alteration of the p53/mdm2 pathway has been reported in the well-differenti ated liposarcoma (WDLS)/dedifferentiated liposarcoma (DDLS) group. We inves tigated the immunoreactivity of p53, mdm2, and p21(WAF1), along with the MI B-1-labeling index (MIB-1-LI) in 21 WDLS and 21 DDLS cases, to clarify the association of these markers with the morphologic changes and the biologica l factors responsible fur the aggressiveness of DDLS. Within DDLS, p53 and p21(WAF1) expression and mdm2 overexpression were significantly more preval ent in the dedifferentiated (DD) components than in the well-differentiated (WD) components. The mdm2 overexpression and p21(WAF1) expression was sign ificantly associated with sclerosing liposarcomas in both WDLS and the WD c omponents of DDLS. There was no significant difference in the immunoreactiv ity of p53, mdm2, or p21(WAF1) or MIB-1-LI between WDLS and the WD componen ts of DDLS. An association was found between p53 expression and mdm2 overex pression in the WD group (comprising WDLS and WD components of DDLS) and in the DD group, significantly so in the WD group. Notably, this correlation was found in the subtype of sclerosing liposarcoma but not in that of lipom a-like liposarcoma. Within DDLS, the clinical outcome of the nonaccessible soft tissue (non-AST: comprising retroperitoneum and mediastinum) group was significantly worse than that of the accessible soft tissue (AST: comprisi ng extremities, buttocks, axilla, and scrotum) group: however. the immunoph enotypes of p53, mdm2, and p21(WAF1) and the MIB-1-LI showed no correlation with survival in the AST group alone, in the non-AST group alone, or in th e 2 together. This study suggests that the immunoreactivity of p53, mdm2, a nd p21(WAF1) is associated With the morphologic changes, but not with the b iological factors responsible for rile aggressiveness of DDLS.