Effects of thymidine phosphorylase levels in cancer, background mucosa, and regional lymph nodes on survival of advanced gastric cancer patients receiving postoperative fluoropyrimidine therapy

Abstract

Due to the contradictory roles that thymidine phosphorylase (TP) plays in both tumor aggressiveness and fluoropyrimidine activation, its impact on drug responses has yet to be clearly established. Therefore, the present study was performed to clarify the effects of TP levels on the prognosis of gastric cancer patients treated postoperatively with different fluoropyrimidines. A total of 52 gastric cancer patients who underwent gastrectomy from January 1997 to March 1998 were enrolled in the present study. The TP levels in the specimens were assayed by enzyme-linked immunosorbent assay (ELISA). Survival was significantly poorer for the 27 patients with high normal tissue TP activity than for the 25 with low normal tissue TP activity. Normal tissue TP level showed different effects on survival according to the chemotherapy regimen used. While the survival rate was significantly poorer in patients with high normal TP level than in those with low normal TP in the 5-FU group, the rate was almost the same in the 5'-DFUR group. Cox's proportional hazard model revealed that tumor TP was an independent prognostic factor in gastric cancer patients. Since activating and catabolizing enzymes for fluoropyrimidines differ from each other, alterations in gene expression of these enzymes should be useful predictive factors.