Thymidylate synthase and dihydropyrimidine dehydrogenase are upregulated in pancreatic and biliary tract cancers

Pathobiology. 2009;76(4):193-8. doi: 10.1159/000218335. Epub 2009 Jun 29.

Abstract

Purpose: To investigate a rationale of pancreatobiliary cancers, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) concentrations in cancer tissues were evaluated.

Patients and 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).

Discussion: 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.

MeSH terms

  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / therapeutic use
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / enzymology
  • Bile Duct Neoplasms / surgery
  • Biliary Tract Neoplasms / drug therapy
  • Biliary Tract Neoplasms / enzymology*
  • Biliary Tract Neoplasms / surgery
  • Dihydrouracil Dehydrogenase (NADP) / metabolism*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / physiology
  • Fluorouracil / metabolism
  • Fluorouracil / therapeutic use
  • Gallbladder Neoplasms / drug therapy
  • Gallbladder Neoplasms / enzymology
  • Gallbladder Neoplasms / surgery
  • Humans
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Thymidylate Synthase / metabolism*
  • Up-Regulation

Substances

  • Antimetabolites, Antineoplastic
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Fluorouracil