MUTATION AND OVEREXPRESSION OF THE P53 TUMOR-SUPPRESSOR GENE FREQUENTLY OCCURS IN UTERINE AND OVARIAN SARCOMAS

Objective: To determine the frequency of mutation and overexpression o f the p53 tumor suppressor gene in female genital tract sarcomas. Meth ods: Immunostaining for p53 was performed in frozen sections of 46 ova rian and uterine sarcomas. Single-stranded conformation polymorphism a nalysis of exons 4-9 of the p53 gene was performed in 33 sarcomas. We performed DNA sequencing of the p53 gene in 22 cases in which we found p53 protein overexpression and/or shifted bands on single-stranded co nformation polymorphism analysis. Results: Overexpression of p53 was s een in 27 of 46 sarcomas (59%), including 26 of 41 (63%) mixed mesoder mal tumors, one of four (25%) leiomyosarcomas, and zero of one endomet rial stromal sarcoma. Among the 33 sarcomas subjected to molecular ana lysis, 21 demonstrated mutations in the p53 gene (64%). Eighteen cance rs had a single mutation, whereas three cases showed two mutations in the p53 gene. There was one mutation in exon 4, seven mutations in exo n 5, three mutations in exon 6, six mutations in exon 7, six mutations in exon 8, and one mutation in exon 9. With the exception of one micr odeletion, which predicted a truncated protein product, all of the mut ations were missense point mutations. All but one of the point mutatio ns resulted in changes in the predicted amino acid sequence. There wer e 18 transition mutations (75%), five transversions (21%), and one del etion (4%). Conclusions: Mutation of the p53 tumor suppressor gene, wi th resultant overexpression of p53 protein, frequently occurs in ovari an and uterine sarcomas. Because most of the mutations are transitions , p53 mutations in these cancers likely arise from spontaneous errors in DNA synthesis and repair rather than from exposure to carcinogens. (Obstet Gynecol 1994;83:118-24)