MUTATION OF THE KI-RAS PROTOONCOGENE IN HUMAN ENDOMETRIAL HYPERPLASIAAND CARCINOMA

Previous studies have demonstrated that some human endometrial carcino mas contain an activating point mutation in codon 12 of the Ki-ras pro tooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we anal yzed 89 samples of premalignant endometrial hyperplasia and an additio nal 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyper plasia, simple, complex, and atypical, with no clear evidence of a dif ferential distribution in any particularly. Furthermore, the overall i ncidence of Ki-ras mutations in the hyperplasia specimens (16%) was si milar to the incidence detected in carcinomas (18%), indicating that r as mutation may represent an early event in a subset of endometrial ca rcinomas. When the tissue samples were segregated as to country of ori gin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United Sta tes, where the incidence, clinicopathological characteristics, and ris k factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathologic al, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from d isease, suggesting that this molecular feature may characterize a subs et of endometrial carcinomas with a good prognosis.