K-ras mutations in endometrial carcinomas with microsatellite instability

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Abstract
K‐ras mutations are known to occur in hyperplasias and carcinomas of the endometrium. No clear correlation has been found yet between K‐ras mutations and microsatellite instability (MI) in these lesions. Fifty‐eight endometrial 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 11 ECs (18.9%). All 11 tumours were endometrioid carcinomas. K‐ras mutations were more frequent 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 tumours but in only one of the five MI‐negative carcinomas. K‐ras mutation was identified in only one atypical EH (1/22, 4.5%); in this case, the EH co‐existed with EC and both lesions exhibited MI. The results support a close relationship between K‐ras mutations and the phenomenon of MI 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 with MI. Copyright © 2000 John Wiley & Sons, Ltd.