Prediction of Response to 5′-Deoxy- 5-Fluorouridine (5′-DFUR) in Patients with Inoperable Advanced Gastric Cancer by Immunostaining of Thymidine Phosphorylase/Platelet-Derived Endothelial Cell Growth Factor

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Abstract
Background: No reliable method is available for predicting the response to chemotherapy in patients with gastric cancer. The anticancer drug 5′-deoxy-5-fluorouridine (5′-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase). We studied the relation between the expression of dThdPase in tumor tissue and the response to treatment with 5′-DFUR to determine if this enzyme can be used to predict the response to chemotherapy. Methods and Materials: We performed endoscopic biopsy and studied the expression of dThdPase by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with inoperable advanced gastric carcinomas before they received multiple-drug chemotherapy, including 5′-DFUR. The relation between the expression of dThdPase and the response to chemotherapy was studied. We also studied the characteristics of positive cells against anti-dThdPase monoclonal antibody. Results: The response rate among patients whose tumors were positive for dThdPase expression (56.8%, 21/37) was higher than that among patients whose tumors were negative for dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing dThdPase were sporadically seen surrounding cancer nests in some patients. Multiple-antibody immunostaining suggested that these spindle-shaped cells were perivascular mesenchymal cells. The response rate was 82.4% (14/17) among patients with spindle-shaped cells strongly positive for dThdPase, as compared with 29.2% (7/24) among those with spindle-shaped cells weakly positive or negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells darkly stained with dThdPase was the factor most strongly related to the response to chemotherapy (odds ratio = 35.513, p = 0.0027). Conclusions: The expression of dThdPase in stromal spindle-shaped cells may be a useful index in predicting the response to 5′-DFUR in patients with gastric cancer.