MOLECULAR ABNORMALITIES OF MDM2 AND P53 GENES IN ADULT SOFT-TISSUE SARCOMAS

Genetic alterations in the p53 and mdm2 genes have been reported to oc cur in soft tissue sarcomas. This study was designed to determine the prevalence and potential clinical value of detected molecular abnormal ities and altered patterns of expression of mdm2 and p53 genes in adul t soft tissue sarcomas. A cohort of 211 soft tissue sarcomas from adul ts that were both clinically and pathologically well characterized was analyzed. Monoclonal antibodies directed against mdm2 and p53 protein s were used to measure overexpression of these proteins in the nuclei of cells from sections of these tumors. Seventy-six of 207 tumors had abnormally high levels of mdm2 proteins and 56 of 211 tumors overexpre ssed p53 protein. Twenty-two cases had abnormally high levels of both mdm2 and p53 proteins based upon immunoreactivity with these antibodie s. There was a striking statistically significant correlation between the overexpression or p53 and mdm2 proteins in the same tumor and poor survival (P < 0.05) of the patients. A group of 73 soft tissue sarcom as was chosen for analysis using Southern blots, single strand conform ation polymorphisms, and direct DNA sequencing to confirm mdm2 gene am plifications and p53 mutations and correlate these with the results of the immunoreactivities. The overexpression of p53 and mdm2 proteins i n the nuclei of tumor cells did not always correlate well with gene am plification at the mdm2 locus or mutation at the p53 gene. The possibl e reasons for these discrepancies are discussed.