Expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53 and p21 in metastatic liver tumor from colorectal cancer after 5-fluorouracil-based chemotherapy.
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.


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.


CONCLUSIONS
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.
Yamagishi
Shigeru
S
Yokohama City University Graduate School of Medicine, Department of Gastroenterological Surgery, Yokohama, Japan. s-gishi@kmc.mhc.east.ntt.co.jp
Shimada
Hiroshi
H
Ishikawa
Takashi
T
Fujii
Shouichi
S
Tanaka
Kuniya
K
Masui
Hidenobu
H
Yamaguchi
Shigeki
S
Ichikawa
Yasushi
Y
Togo
Shinji
S
Ike
Hideyuki
H
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil; D006499:Hepatic Artery; D006801:Humans; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D015689:Oncogene Protein p21(ras); D005472:Fluorouracil