p53 gene mutations and p53 protein expression in human soft tissue sarcomas

To determine the frequency of mutation and overexpression of the p53 tumor suppressor gene in human soft tissue sarcomas.

A total of 31 soft tissue sarcomas were analyzed by immunohistochemistry for the expression of p53 protein and were subsequently investigated by the polymerase chain reaction technique and direct sequence analysis of exons 5 through 8 in the p53 gene.

The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea.

Thirty-one patients with soft tissue tumor were surgically treated and diagnosed as having either malignant fibrous histiocytoma, rhabdomyosarcoma, or leiomyosarcoma.

Overexpression of p53 was seen in 17 (55%) of 31 sarcomas, including 9 (64%) of 14 malignant fibrous histiocytomas, 4 (44%) of 9 rhabdomyosarcomas, and 4 (50%) of 8 leiomyosarcomas. Seven cases (23%) demonstrated mutations in the p53 gene. Six had a single mutation, whereas one showed triple mutations. There were seven mutations in 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 sequence. Among the nine mutations, seven (78%) were transversions and two (22%) were transitions.

Mutation of the p53 tumor suppressor gene, with resultant overexpression of p53 protein, frequently occurs in human soft tissue sarcomas, supporting the role of p53 mutations in the pathogenesis of soft tissue sarcoma and the possible usefulness of p53 immunolocalization as a screening method for p53 mutations.