MUTATION OF THE P53 TUMOR-SUPPRESSOR GENE IS NOT A FEATURE OF ENDOMETRIAL HYPERPLASIAS

OBJECTIVE: Mutation and overexpression of the p53 gene occur in approx imately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we e xamined the p53 gene in endometrial hyperplasias. STUDY DESIGN: Genomi c deoxyribonucleic acid was extracted from 117 endometrial hyperplasia s (36 simple, 40 complex, 41 atypical) and 30 endometrial cancers. Exo ns 5 through 8 of the p53 gene were amplified by means of the polymera se chain reaction. Mutations in the p53 gene were sought with single-s tranded conformation polymorphism analysis and confirmed by direct deo xyribonucleic acid sequencing. RESULTS: None of 117 endometrial hyperp lasias were found to have mutations in the p53 gene, whereas mutations were seen in three of 30 (10%) endometrial cancers (p < 0.02). The p5 3 mutations seen in three cancers were confirmed by direct sequencing (codons 157, 180, 272). CONCLUSION: Because it does not appear to be a feature of endometrial hyperplasias, mutation of the p53 gene may rep resent a relatively late event in endometrial carcinogenesis.