A newly identified pattern of K-ras mutations at codons 12 and 13 is associated with long-term survival in colorectal cancer

Abstract

Background . Although K-ras mutations reportedly occur in 40% to 60% of all colorectal carcinomas, the relationship between specific mutations and clinical outcome is unclear. The purpose of this study was to assess the frequency and types of K-ras mutations in 89 colorectal cancer patients, comparing groups with short-term (less than 5 years) and long-term (more than 10 years) survival. Methods . The group was divided into four cohorts by survival and modified Dukes classification (Dukes B 2 and C 2). DNA was extracted from formalin-fixed paraffin-embedded archival material. Mutational status was analyzed using a modification of allele-specific-polymerase chain reaction. Results . Mutations in codon 12 were found in 11.2% of tumors, and 83% of tumors had mutations in codon 13. Gly > Asp accounted for 85.2% of the mutations. Tumors with mutations in both codon 12 and codon 13 occurred significantly more frequently in the long-term (21.3%) versus the short-term (2.4%) survival group. Gly > Asp mutations in either codon were related to long-term survival, and 80% of long-term survivors with mutations in both codons had Gly > Asp mutations in both. Conclusions . Simultaneous mutation in codons 12 and 13 of the K-ras gene appears to be a positive prognostic indicator in colorectal cancer.