PT  - JOURNAL ARTICLE
AU  - G L Mutter
AU  - H Wada
AU  - W C Faquin
AU  - T Enomoto
TI  - K-ras mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis.
AID  - 10.1136/mp.52.5.257
DP  - 1999 Oct 01
TA  - Molecular Pathology
PG  - 257--262
VI  - 52
IP  - 5
4099  - http://mp.bmj.com/content/52/5/257.short
4100  - http://mp.bmj.com/content/52/5/257.full
SO  - Mol Pathol1999 Oct 01; 52
AB  - AIMS: Sequential events of endometrial tumorigenesis can be studied by comparison of genetic lesions seen in normal, premalignant, and malignant tissues. The distribution of k-ras mutations in microsatellite stable and unstable premalignant lesions was studied to determine whether this gene is implicated in both tumorigenic pathways. METHODS: K-ras mutations were analysed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing in matched endometrial normal, premalignant (atypical hyperplasias), and adenocarcinoma tissues from individual patients. Identification of precancers solely by their appearance as atypical endometrial hyperplasias is very subjective; therefore, in addition to histopathological assessment, we performed molecular testing (non-random X inactivation or clonal altered microsatellites) for an expected feature of precancers--that is, monoclonality. RESULTS: Equivalent K-ras mutation frequencies were seen in microsatellite stable (six of 33) and unstable (three of 23) cancers. In both types, K-ras mutation in monoclonal precancers usually corresponded to a change from normal to an equivocal (two of 12) or hyperplastic (10 of 12) histology. Divergent K-ras genotypes among multiple neoplastic tissues of individual patients (two of six patients) are exceptions explained either by multicentric premalignant disease, or acquisition of K-ras mutation late in neoplastic progression. CONCLUSIONS: K-ras mutation occurs in both premalignant microsatellite stable and unstable endometrial neoplasia, sometimes before acquisition of features readily diagnostic as atypical endometrial hyperplasia.