[Thymidylate synthase and dihydropyrimidine dehydrogenase expression and histological effects of preoperative UFT in gastric cancer patients].

UNLABELLED

During DNA synthesis in tumors, fluoropyrimidine anticancer agents target thymidylate synthase (TS) that catalyze the synthesis of dTMP from dUMP and are metabolized by dihydropyrimidine dehydrogenase (DPD). We administered UFT to patients with gastric cancer preoperatively to prevent cancers from advancing while they await surgery or down staging.

PATIENTS AND METHODS

We administered UFT to 24 gastric cancer patients at 360 mg/m(2)/day for longer than 3 weeks as a preoperative chemotherapy. TS and DPD expression in the tumor were measured by immunohistochemistry staining before and after (during surgery) chemotherapy and compared with the results of histological assessment.

RESULTS

TS and DPD expression decreased significantly after UFT administration (p<0.05). Histological assessment showed Grade 1 b or 2 in 11 of 24 patients (46%). Eight of 15 patients with high DPD (53.3%) exhibited Grade 1 b or 2.

CONCLUSIONS

Histological assessment revealed the efficacy of UFT, through a DPD-inhibitory fluoropyrimidine (DIF) effect, in patients with high DPD. This suggests that preoperative administration of UFT can be a useful clinical measure.