K-ras mutations in endometrial carcinomas with microsatellite instability

K-ras mutations are known to occur in hyperplasias and carcinomas of the en dometrium. No clear correlation has been found yet between K-ras mutations and microsatellite instability (MI) in these lesions. Fifty-eight endometri al carcinomas (ECs) and 22 endometrial hyperplasias (EHs) were analysed for K-ras mutation by single-strand conformational polymorphism analysis (SSCP ), restriction analysis, and DNA sequencing. MI status had been established previously at five dinucleotide loci and was reconfirmed with markers BAT- 25 and BAT-26 by SSCP. K-ras mutations were detected in II ECs (18.9%). All II tumours were endometrioid carcinomas. Ii-ras mutations were more freque nt in MI-positive (6/14, 42.8%) than in MI-negative tumours (5/44, 11.3%) ( p=0.017), Methylation-related transitions were detected in five of the six MI-positive rumours but in only one of the five MI-negative carcinomas, li- ras mutation was identified in only one atypical EH (1/22, 4.5%); in this c ase, the EH co-existed with EC and both lesions exhibited MI, The results s upport a close relationship between K-ras mutations and the phenomenon of M I in endometrial carcinomas, The frequent occurrence of methylation-related transitions in these tumours may indicate a cause-effect relationship with the altered methylation status which has been described in association wit h MI, Copyright (C) 2000 John Wiley & Sons, Ltd.