Background: Orotate phosphoribosyltransferase (OPRT; EC 2.4.2.10), a key enzyme that catalyzes one of the primary steps in the phosphorylation of fluoropyrimidine, was recently recognized as an important enzyme that determines the anticancer effects of the dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1.
Methods: Levels of OPRT were examined in 97 gastric carcinoma tissues and 65 normal gastric mucosa tissues obtained from patients with gastric carcinoma. The relation between OPRT levels and clinicopathological variables was evaluated, and correlations of OPRT with thymidylate synthase and dihydropyrimidine dehydrogenase levels in gastric carcinoma tissues were evaluated.
Results: Although OPRT levels were high in well-differentiated and localized carcinomas, they were not correlated with other clinicopathological variables or with the pathological stage of gastric carcinoma. Levels of OPRT were significantly higher in gastric carcinoma tissue than in normal gastric mucosa. OPRT levels were not correlated with levels of either thymidylate synthase or dihydropyrimidine dehydrogenase. In samples of gastric carcinoma tissues and normal gastric mucosa tissues obtained simultaneously from 24 patients, no correlation was found between OPRT levels in gastric carcinoma and levels in normal gastric mucosa.
Conclusion: These results suggest that the OPRT level is significantly higher in gastric carcinoma tissue than in normal gastric mucosa and that the OPRT level in gastric carcinoma is a novel variable that is independent of the levels of other previously known enzymes related to 5-fluorouracil (FU) metabolism.