Role of thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumour progression and sensitivity to doxifluridine in gastric cancer patients

Abstract

This study was designed to investigate the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) on tumour progression and sensitivity to 5′-deoxy-5-fluorouridine (5′-DFUR). Tumour tissue was obtained from surgically resected samples from 93 patients with primary gastric cancer. Tumour TP and DPD expression levels were determined by the enzyme-linked immunosorbent assay (ELISA) system and compared with several clinicopathological factors and in vitro sensitivity to 5′-DFUR. DPD showed no correlation with any clinicopathological factors. However, the TP level was significantly correlated with the depth of tumour, lymphatic invasion and venous invasion. In comparison with 5′-DFUR sensitivity, there was a weak inverse correlation between the DPD level and the sensitivity to 5′-DFUR (rs=−0.361). Furthermore, the TP/DPD ratio showed a significant correlation with 5′-DFUR sensitivity (rs=0.634). In a subgroup of patients with postoperative 5′-DFUR administration, the survival rate was significantly better in patients with a high TP/DPD ratio (n=8) than in those with low TP/DPD ratio (n=14) (P=0.0140). These results suggest that sensitivity to 5′-DFUR is predictable by measurement of both TP and DPD levels.