K-ras mutations in endometrial carcinomas with microsatellite instability

J Pathol. 2001 Feb;193(2):193-9. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH769>3.0.CO;2-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / genetics*
  • DNA Methylation
  • Endometrial Hyperplasia / genetics
  • Endometrial Neoplasms / genetics*
  • Female
  • Genes, ras / genetics*
  • Humans
  • Microsatellite Repeats / genetics*
  • Mutation / genetics*
  • Polymorphism, Single-Stranded Conformational
  • Sequence Analysis, DNA