K-ras mutations and prognosis in large-bowel carcinomas

Background: Colorectal carcinogenesis is regarded as a multistep process involving several genetic alterations, with mutation in the K-ras gene in about half of the tumours. We aimed at clarifying the role of this genetic alteration related to survival and clinicopathologic variables. Methods: One hundred large bowel carcinomas operated on between 1978 and 1982 were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene, using enriched polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing. Results: Forty mutations were found (40%): 31 in codon 12 and 9 in codon 13, 7 different types. There was no relationship between tumours with and without K-las mutations with regard to Dukes' stages, age or sex of the patient, tumour localization, histologic grade, DNA ploidy pattern, HLA-DR staining pattern, or survival. Samples from 5 different localizations in 7 carcinomas showed identical K-ras mutation pattern, as did 19 recurrences/metastases originating from 11 carcinomas. Conclusions: When present, the primary tumour shows homogeneous distribution of K-ras mutation, and the mutation follows the carcinoma in the secondary deposit, regardless of lymphogenous or hematogenous spread. The presence of K-ras mutation does not seem to have prognostic significance for the patient, and the precise nucleotide change is furthermore not predictive of tumour behaviour.