K-ras mutations in endometrial carcinomas with microsatellite instability

Helena Lagarda, Lluis Catasus, Rosmary Arguelles, Xavier Matias-Guiu, Jaime Prat

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109 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)193-199
JournalJournal of Pathology
Volume193
Issue number2
DOIs
Publication statusPublished - 15 Feb 2001

Keywords

  • Carcinogenesis
  • Endometrial carcinoma
  • Endometrioid carcinoma
  • K-ras
  • Microsatellite instability
  • Molecular pathology
  • Mutations

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