Prognostic significance of K-ras mutations in colorectal carcinoma.

Mutations at codons 12, 13, and 61 of the ras genes have been found in a variety of human tumors and may have prognostic significance. K-ras mutations have been shown in 40%-50% of colorectal cancers. Using a simple nonradioactive polymerase chain reaction-based technique, we have investigated the possible prognostic significance of point mutations of the K-ras gene in patients with human colorectal carcinomas. The prevalence and the type of ras mutations were compared between a group of 35 patients having recurrent disease within 5 years and a group of 64 patients who were disease free 5 years following surgery. First, we found that the overall prevalence of mutations within codons 12 and 13 of the K-ras gene was 25% in the nonrecurring group vs. 71% in the patients with recurrent disease (P < 0.0001) and, second, that mutations other than GGT to GAT occurred, with one exception, exclusively in recurring tumors. In Dukes' B and C primary tumors, mutations other than GGT to GAT identify patients at very high risk for recurrence. Our results indicate that determining the K-ras mutations provides a good prognostic factor in patients with advanced colorectal carcinoma.