P53 GENE-MUTATIONS AND P53 PROTEIN EXPRESSION IN HUMAN SOFT-TISSUE SARCOMAS

Objective.-To determine the frequency of mutation and overexpression o f the p53 tumor suppressor gene in human soft tissue sarcomas. Design. -A total of 31 soft tissue sarcomas were analyzed by immunohistochemis try for the expression of p53 protein and were subsequently investigat ed by the polymerase chain reaction technique and direct sequence anal ysis of exons 5 through 8 in the p53 gene. Setting.-The specimens were collected over a 3-year period in the laboratories at our large teach ing hospital in Seoul, Republic of Korea. Patients.-Thirty-one patient s with soft tissue tumor were surgically treated and diagnosed as havi ng either malignant fibrous histiocytoma, rhabdomyosarcoma, or leiomyo sarcoma. Results.-Overexpression of p53 was seen in 17 (55%) of 31 sar comas, including 9 (64%) of 14 malignant fibrous histiocytomas, 4 (44% ) of 9 rhabdomyosarcomas, and 4 (50%) of 8 leiomyosarcomas. Seven case s (23%) demonstrated mutations in the p53 gene. Six had a single mutat ion, whereas one showed triple mutations. There were seven mutations i n exon 5, one in exon 6, and one in exon 7. All of the mutations were missense mutations, resulting in changes in the predicted amino acid s equence. Among the nine mutations, seven (78%) were transversions and two (22%) were transitions. Conclusions.-Mutation of the p53 tumor sup pressor gene, with resultant overexpression of p53 protein, frequently occurs in human soft tissue sarcomas, supporting the role of p53 muta tions in the pathogenesis of soft tissue sarcoma and the possible usef ulness of p53 immunolocalization as a screening method for p53 mutatio ns.