Determination of microsatellite instability, p53 and K-RAS mutations in hepatic metastases from patients with colorectal cancer: relationship with response to 5-fluorouracil and survival.

摘要: In vitro and clinical studies have suggested that high-frequency microsatellite instability (MSI-H) phenotype, p53 K-ras mutations might influence the response to chemotherapy in a variety of tumors, including primary colorectal cancers (CRC). Unresectable hepatic metastases from CRC are commonly treated with 5-fluorouracil (5FU) folinic acid. Since several new active drugs now used for treating CRC, molecular determinants predictive 5FU would thus be crucial optimizing indications those patients. MSI-H status were characterized prospective study 56 patients metastatic liver 5FU-based chemotherapy. The objective rate after 3-month treatment was 32.1%. prevalence mutations, phenotype 62.5%, 30.3% 1.8%, respectively. No significant association found between (78% mutated tumors responders vs. 55% nonresponders; p = 0.10) (39% 26% 0.34). Survival longer p53-mutated than unresected wild-type (median survival 15 months 17 months; 0.06). determination does not discriminate group should preferentially benefit prognosis is better when mutated.