Roles of Thymidylate Synthase and Dihydropyrimidine Dehydrogenase in Tumor Progression and Sensitivity to 5-fluorouracil in Human Gastric Cancer

Anticancer Res. Mar-Apr 2002;22(2A):761-8.

Abstract

Background: The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated.

Materials and methods: TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay.

Results: There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465).

Conclusion: These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / pharmacology*
  • Chemotherapy, Adjuvant
  • Dihydrouracil Dehydrogenase (NADP)
  • Disease Progression
  • Drug Screening Assays, Antitumor
  • Female
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Oxidoreductases / metabolism*
  • Predictive Value of Tests
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Thymidylate Synthase / metabolism*

Substances

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