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

In vitro and clinical studies have suggested that high-frequency microsatel lite instability (MSI-H) phenotype, p53 and K-ras mutations might influence the response to chemotherapy in a variety of tumors, including primary col orectal cancers (CRC), Unresectable hepatic metastases from CRC are commonl y treated with 5-fluorouracil (5FU) and folinic acid. Since several new act ive drugs are now used for treating CRC, molecular determinants predictive to response to 5FU would thus be crucial for optimizing indications of chem otherapy to those patients. MSI-H phenotype, p53 and K-ras status were char acterized in a prospective study of 56 patients with CRC metastatic to the liver and treated with 5FU-based chemotherapy, The objective response rate after a 3-month treatment was 32.1%, The prevalence of p53 mutations, K-ras mutations and MSI-H phenotype was 62.5%, 30.3% and 1.8%, respectively, No significant association was found between response to chemotherapy and p53 mutations (78% mutated tumors in responders vs. 55%. in nonresponders; p = 0.10) and K-ras mutations (39% mutated tumors in responders vs. 26% in nonr esponders; p = 0.34), Survival was longer for patients with p53-mutated met astases than for patients with unresected wild-type p53 metastases (median survival 15 months vs. 17 months; p = 0.06), The determination of the MSI-H phenotype, p53 and K-ras status in hepatic metastases from CRC does not di scriminate a group of patients that should preferentially benefit from 5FU- based chemotherapy. The prognosis of patients with treated liver metastases is better when p53 is mutated. (C) 2001 Wiley-Liss, Inc.