Expression of Dihydropyrimidine Dehydrogenase, Thymidylate Synthase, p53 and p21 in Metastatic Liver Tumor from Colorectal Cancer after 5-Fluorouracil-based Chemotherapy

Abstract

Background: The expression of genes thought to be related to 5-FU chemosensitivity has been extensively investigated. However, little data is available on the expression patterns of these genes after chemotherapy. Patients and Methods: We investigated the expression of four genes, DPD, TS, p53 and p21, in the metastatic liver lesions obtained from colorectal cancer patients who had been treated with hepatic arterial infusions of 5-fluorouracil(5-FU)-based chemotherapy. Results: Expression of DPD, TS and p53 in the metastatic liver lesions was significantly higher in the chemotherapy-response group than in the no response group. In the response group, viable cancer cell nests were seen in confined spaces surrounded by fibrous tissue. It was of interest that these cancer cells in the response group showed conspicuous immunoreactivity of DPD, TS and p53. Conclusion: An analysis of genes involved in 5-FU sensitivity revealed that surviving tumor cells exhibited resistance characteristics, indicating that the chemotherapy regimen should be altered, even in partially responding cases, unless the response is pathologically complete.