Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Dukes C colon cancer

PURPOSE: Mutations in K-ras and TP53 genes are common in colorectal cancer. They affect biologic behavior and might influence chemotherapy susceptibil ity in these tumors. We investigated whether the survival of patients with Dukes C colon cancer treated with adjuvant chemotherapy is influenced by K- ras and TP53 mutations. METHODS: Mutation screening of the hut spots of the K-ras gene and of the evolutionarily conserved regions of the TP53 gene wa s performed by denaturing gradient gel electrophoresis technique in formali n-fixed paraffin-embedded specimens of 55 consecutive patients with Dukes C colon cancer treated with adjuvant 5-fluorouracil-based chemotherapy. The median follow-up was 47 (range, 32-66) months. RESULTS: Alterations in the mutation hot spots of K-ras were found at codon 12 (n = 11) and 13 (n = 4) in 15 of the 55 carcinomas (27 percent). No mutation was found at codon GI. Mutations of a probably causative nature in the evolutionarily conserved r egions (exons 5-8) of the TP53 gene were found in 24 tumors (44 percent). K -ras and TP53 mutations mere found equally in the group with recurrent dise ase (7/26 (26 percent) and 12/27 (44 percent), respectively) and in the gro up without recurrences (8/28 (24 percent) and 12/28 (43 percent), respectiv ely). Cancer-specific survival did not differ significantly between patient s with K-ras or TP53 or both mutated and nonmutated tumors, respectively (l og-rank test: K-ras, P = 0.72 and TP53, P = 0.77; K-ras and TP53, P = 0.8). Also, potentially aggressive K-ras codon 12 and 13 mutations had the same survival as tumors without these mutations (log-rank test; P = 0.73). CONCL USIONS: Patients with K-ras or TP53 or both mutated Dukes C colon tumors ha ve the same survival as nonmutated tumors when treated with adjuvant chemot herapy. These data suggest that mutations in K-ras or TP53 alone are not pr ognostic indicators in patients with Dukes C colon cancer receiving adjuvan t 5-Fluorouracil-based therapy.