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

Rosty, Christophe, Chazal, Maurice, Etienne, Marie-Christine, Letoublon, Christian, Bourgeon, André, Delpero, Jean-Robert, Pezet, Denis, Beaune, Philippe, Laurent-Puig, Pierre and Milano, Gérard (2001) 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. International Journal of Cancer, 95 3: 162-167. doi:10.1002/1097-0215(20010520)95:3<162::AID-IJC1028>3.0.CO;2-J


Author Rosty, Christophe
Chazal, Maurice
Etienne, Marie-Christine
Letoublon, Christian
Bourgeon, André
Delpero, Jean-Robert
Pezet, Denis
Beaune, Philippe
Laurent-Puig, Pierre
Milano, Gérard
Title 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
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
1097-0215
Publication date 2001-05
Sub-type Article (original research)
DOI 10.1002/1097-0215(20010520)95:3<162::AID-IJC1028>3.0.CO;2-J
Volume 95
Issue 3
Start page 162
End page 167
Total pages 6
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
In vitro and clinical studies have suggested that high-frequency microsatellite instability (MSI-H) phenotype, p53 and 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) and folinic acid. Since several new active drugs are now used for treating CRC, molecular determinants predictive to response to 5FU would thus be crucial for optimizing indications of chemotherapy to those patients. MSI-H phenotype, p53 and K-ras status were characterized 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 nonresponders; p = 0.34). Survival was longer for patients with p53-mutated metastases 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 discriminate 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.
Keyword Hepatic metastasis
Colorectal cancer
Chemotherapy
p53
K-ras
Microsatellite instability
Prognosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 09 Mar 2011, 14:22:25 EST