HIGH PROGNOSTIC-SIGNIFICANCE OF MDM2 P53 CO-OVEREXPRESSION IN SOFT-TISSUE SARCOMAS OF THE EXTREMITIES/

Soft tissue sarcomas are a heterogenous group of neoplasms with variou s histological subtypes, Up to now, no individual causal molecular mar kers; for prognosis and therapeutic success have been identified, A tu morigenic connection between the oncogene product Mdm2 and tumor suppr essor p53 is generally accepted, but their possible clinical relevance has not yet been investigated sufficiently in soft tissue sarcoma, In 86 primary soft tissue sarcoma of the extremities (RO-resected, T1/2 N0 M0), Mdm2 and p53 overexpression were investigated by immunohistoch emistry. The results were adjusted to clinico-pathological characteris tics and evaluated for their prognostic relevance by multivariate anal ysis, In Cox's multivariate analysis with stratification of Mdm2 to p5 3 results, we determined four groups which had different prognostic va lues for relapse-free and overall survival (Mdm2-/p53-<Mdm2-/p53+<Mdm2 +/p53-<Mdm2+/p53+). The most striking finding was a relative risk (rr) for overall survival of 18.77 (P=0.006) for patients with Mdm2/p53 co -overexpression (n=40). It is noticeably higher than the additive risk from both factors. Coincident Mdm2/p53 overexpression is an independe nt molecular marker with the highest prognostic relevance described fo r soft tissue sarcoma, Thus, a high risk sarcoma group has been define d which we believe requires alternative therapeutic approaches.