Mutation and overexpression of the p53 gene frequently occur in uterine endometrial carcinomas and endometrioid carcinomas of the ovary. To define the pathogenetic relationship between endometrial neoplasms we examined p53 mutations and allelic losses in these diseases. Genomic deoxyribonucleic acid (DNA) was extracted from 12 endometrioid carcinomas of the ovary and 41 adenocarcinomas and 8 adenosquamous carcinomas of the uterus. Exons 4 through 8 of the p53 gene were amplified by means of the polymerase chain reaction. Mutations in each exon were detected with single-strand conformation polymorphism analysis and characterized with nucleotide sequencing analysis. Five (42%) and 6 (75%) of 12 endometrioid carcinomas were found to have mutations in exons 5 and 7, which encode for the functional domains of p53 molecules and allelic loss of exon 4, respectively. All these patients with aberrant p53 presented at an advanced clinical disease stage. Eighteen percent of the endometrial carcinomas demonstrated a random mutation in exons 5 through 7, and no association was observed between the mutation and the clinical stage and histological grade. The finding of different patterns of p53 mutations in endometrial carcinoma and endometrioid carcinoma suggest that each may follow a different molecular developmental pathway.

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