Clinical significance of dihydropyrimidine dehydrogenase  and thymidylate synthase expression in patients  with pancreatic cancer.
BACKGROUND
Little is known about the clinical significance of TS and DPD in pancreatic cancer. We aimed to evaluate TS and DPD expression levels in not only pancreatic cancer but also surrounding normal pancreatic tissues to assess the clinical implications of the expression of TS and DPD in this study.


METHODS
Pancreatic cancer and normal pancreatic tissues were obtained from 18 patients with pancreatic cancer who underwent pancreatic resection to measure TS and DPD activities. The TS and DPD activities were determined by enzyme-linked immunosorbent assay using non-fixed fresh-frozen specimens.


RESULTS
Pancreatic cancer tissues had significantly higher DPD and TS enzyme activities than surrounding normal tissue. Anaplastic ductal carcinoma had higher DPD and TS activities than the other histological types. Patients with high DPD in this study demonstrated poorer prognosis than those with low DPD. On the other hand, there was no statistically significant difference in survival between the high and the low TS groups.


CONCLUSIONS
The efficacy of 5-FU may be lower in pancreatic cancer tissue than in normal tissue because DPD activity is upregulated in pancreatic cancer tissue compared to normal pancreatic tissue. It is necessary to develop an effective 5-FU delivery system and/or 5-FU combined with an inhibitor for DPD that can be used when 5-FU must be administered to patients with pancreatic cancer. High DPD activity may be a prognostic factor in patients with pancreatic cancer.
Nakahara
Osamu
O
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan.
Takamori
Hiroshi
H
Tanaka
Hiroshi
H
Sakamoto
Yasuo
Y
Ikuta
Yoshiaki
Y
Furuhashi
Satoshi
S
Watanabe
Masayuki
M
Beppu
Toru
T
Hirota
Masahiko
M
Kanemitsu
Keiichiro
K
Baba
Hideo
H
D000368:Aged; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000401:mortality; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism*
D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase