Clinical impact of thymidine phosphorylase expression in gastric cancer

Thymidine phosphorylase (dThdPase) is an enzyme that is involved in pyrimidine nucleoside metabolism and DNA synthesis and converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU). The aim of this study was to elucidate the relationship between dThdPase expression and biological malignancy, prognosis, and sensitivity to postoperative chemotherapy, using immunohistochemical staining. We studied 148 patients with gastric cancer who underwent surgery at Department of Surgery II in Oita Medical University between 1990 and 1999. Immunohistochemical expression of dThdPase was correlated to clinicopathological factors and postoperative survival. Tumor tissue was dThdPase-positive in 112 patients. The results suggested a relationship between the degree of histological differentiation and dThdPase expression (p=0.0697). Examination of dThdPase expression based on the site of the tumor revealed that the groups with upper or lower gastric cancer included a significantly greater number of dThdPase-positive patients (p=0.0011). Analysis of the patients as a whole showed no significant difference between the survival. In the chemotherapy group, the dThdPase-positive patients tended to have a more favorable prognosis than the dThdPase-negative patients (p=0.0578). The results suggest that postoperative adjuvant chemotherapy that makes use of FU metabolic pathways may improve prognosis in patients with dThdPase-positive gastric cancer.