Retrospective study on thymidylate synthase as a predictor of outcome and sensitivity to adjuvant chemotherapy in patients with curatively resected colorectal cancer

We carried out a retrospective evaluation of thymidylate synthase (TS) expression in tumor tissue, and its relation to outcome and response to treatment. The treatment consisted of chemotherapy with tegafur and uracil (UFT). The study group comprised 245 patients with curatively resected Dukes' stage B or C colorectal cancer who were postoperatively enrolled in a controlled study and assigned to receive UFT or no adjuvant chemotherapy. TS expression in tumor tissue was evaluated immunohistochemically with the use of recombinant human TS-specific antibody. Results were as follows. There was no relation between TS expression and the rate of 5-year disease-free survival. Similar results were obtained in both colonic and rectal tumors. The rate of 5-year disease-free survival was significantly higher in the UFT group than in the group receiving no adjuvant chemotherapy (p=0.0055).The difference in survival became more marked among patients whose tumors had diffuse TS expression (p=0.0027). There was no difference in survival between the treatment groups among patients whose tumors had focal TS expression. We conclude that, although unrelated to outcome, TS activity may be useful in predicting the response to adjuvant chemotherapy with UFT in patients with curatively resected Dukes' stage B or C colorectal cancer.