Distinctive clinicopathological features of Ki-ras mutated colorectal cancers.

BACKGROUND AND OBJECTIVES: We explored the relationship between the mutation pattern of Ki-ras and the clinicopathological features of colorectal cancers (CRCs).
METHODS: Relationships between clinicopathological parameters and Ki-ras mutation status were analyzed in 255 CRC patients using the chi-square and student t-tests. Kaplan-Meier survival curves were compared using the log-rank test.
RESULTS: Ki-ras mutation occurred in 43.9% of tumors, and 83% affected codon 12. The most frequent mutations were GGT->GAT (Gly->Asp) (37.5%), followed by GGT->GTT (Gly->Val) (31.3%), both in codon 12. The frequency of Ki-ras mutation was similar for different tumor stages (38.2-47.8%). The mucin component of tumors was significantly associated with Ki-ras mutation. The 4-year overall and disease-free survival was 61% and 54%, respectively, for patients with Ki-ras mutated tumors, and 73% and 60% for patients with nonmutated tumors (not statistically significant). Patients with Ki-ras mutated tumors had lower plasma folate (24 ng/dl) than those bearing nonmutated tumors (37 ng/dl). Patients with G->T Ki-ras mutations had the lowest folate level (22 ng/dl), followed by those with G->A mutations (25 ng/dl).
CONCLUSIONS: Ki-ras mutated colorectal tumors have a higher mucin production and higher differentiation, and are associated with lower plasma folate levels and a relatively poorer disease outcome. 2006 Wiley-Liss, Inc.