Cancer Res  1992 May 15;52(10):2777-81 

Clinical implications of K-ras mutations in malignant epithelial tumors of the
endometrium.

Mizuuchi H, Nasim S, Kudo R, Silverberg SG, Greenhouse S, Garrett CT.

Department of Pathology, George Washington University, Washington, DC 20037.

Tumorigenesis in humans and experimental animals appears to involve the
activation of ras protooncogenes for a number of organ systems and seems to be
important to the development of the metastatic phenotype in several model
systems. Clinically, the presence of activated ras protooncogenes has been
reported to be a negative prognostic factor in the myelodysplastic syndrome and
in adenocarcinoma of the lung. In the present study we examined 49 cases of
endometrial carcinoma for mutations in the first exon of K-ras using the
polymerase chain reaction and direct sequencing. Mutations in codon 12 or 13 of
K-ras were detected in 6 of 49 cases (12.2%). These six cases consisted of five
endometrioid endometrial carcinomas, each of which had a mutation in codon 12,
and one case of clear cell carcinoma, which had a mutation in codon 13. In our
study the presence of mutations in K-ras appeared to be an unfavorable
prognostic factor. Three of six patients with the mutation died during
follow-up, while only 7% of the 43 patients without K-ras mutations expired
during this same period. In multivariate analysis using the Cox proportional
hazard model, K-ras activation appeared to be an independent risk factor when
compared with clinical stage, depth of myometrial invasion, and patient age.
Thus, our findings support the hypothesis that K-ras protooncogene activation
plays an important role in determining the aggressiveness of endometrial
carcinoma.

PMID: 1581890 [PubMed - indexed for MEDLINE]