Ki-ras mutation type and the survival benefit from adjuvant chemotherapy in Dukes' C colorectal cancer

Ki-ras mutations are associated with an increased risk of relapse and death in colorectal cancer (CRC) patients, with some mutations being more aggres sive than others. The present study examined the predictive value of differ ent Ki-rus mutation types in a retrospective series of 430 Dukes' C stage C RC patients, of whom 208 (48%.) had received adjuvant chemotherapy with 5-f luorouracil/levamisole or 5-fluorouracil/leucovorin. A total of 140 mutatio ns were detected, the majority (58%, 81/140) being glycine to aspartate mut ations in codons 12 and 13. Glycine to valine mutations in codon 12 (14%, 2 0/140) and other less frequent, non-specified mutation types (28%, 39/140) accounted for the remaining mutations. Kaplan-Meier survival analysis revea led that both Ki-ras wild-type and mutant patient groups derived significan t survival benefit from chemotherapy. However, when patients were stratifie d according to the type of mutation, those with non-aspartate mutations app eared to gain more benefit from this treatment than those with aspartate mu tations. Multivariate analysis that included other possible predictive fact ors in Dukes' C CRC (tumour site, patient sex, TP53 mutation) demonstrated that non-aspartate mutations in particular were associated with a significa nt survival benefit from chemotherapy (HR = 0.11, 95%, CI: 0.04-0.30, p < 0 .001). These results suggest that the type of Ki-ras mutation could be a cl inically useful molecular marker for the identification of CRC subgroups th at are likely to benefit from 5-fluorouracil-based adjuvant chemotherapy. C opyright (C) 2001 John Wiley & Sons, Ltd.