Thymidylate synthase and dihydropyrimidine dehydrogenase are upregulated in pancreatic and biliary tract cancers.
OBJECTIVE
To investigate a rationale of pancreatobiliary cancers, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) concentrations in cancer tissues were evaluated.


METHODS
Twenty-nine patients with pancreatic cancer (PC) and 43 with biliary tract cancer (BTC; 27 cases of bile duct cancer, 8 of gallbladder cancer and 8 of cancer of the papillary area) were included. ELISA was used to assess the concentrations of TS and DPD in cancerous and noncancerous tissues. All 82 patients were followed up at least 12 months after surgery. We compared patient survivals between the 2 groups, taking TS and DPD cutoff as median values, high versus low DPD and high versus low TS in the cancerous tissue of PC and BTC patients.


RESULTS
As for PC, DPD and TS concentrations were significantly higher in cancerous than in noncancerous tissues (p = 0.016 vs. 0.036). In BTC, TS concentration was higher in cancerous than in noncancerous tissue (p = 0.0001). Patients with low TS and DPD concentrations had a tendency to have a better disease-free survival than those with high TS and DPD concentrations in PC groups; especially, BTC patients' disease-free survival with high TS was significantly longer than that with low TS (p = 0.0083).


CONCLUSIONS
TS and DPD levels had a tendency to be high in PC and BTC cancerous tissues. High TS in the cancerous tissue was associated with better disease-free survival in BTC.
Shimoda
Mitsugi
M
Second Department of Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan. mshimoda@dokkyomed.ac.jp
Sawada
Tokihiko
T
Kubota
Keiichi
K
D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000601:surgery; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000601:surgery; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism*; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil