Objectives: Thymidylate synthase (TS), a key enzyme in DNA synthesis, is overexpressed in a variety of cancer cells. 5-Fluorouracil (5-FU), an anticancer agent used clinically against various cancers, including prostate cancer, inhibits DNA synthesis by binding TS. In this study, we investigated the expression of TS in prostate cancer and its prognostic significance. Its association with the expression of dihydropyrimidine dehydrogenase (DPD), a principal enzyme in the degradation of 5-FU and pyrimidine nucleotides, was also examined. Methods: Fifty-two prostatic tissue specimens were obtained from patients who had undergone radical prostatectomy for prostate cancer without neoadjuvant hormonal therapy. We analyzed the cancerous tissue and normal prostatic tissue specimens for TS expression using immunohistochemistry. Results: TS was expressed at greater levels in the prostate cancer specimens than in the normal prostatic tissue specimens. The patients with prostate cancer with negative TS expression had a longer postoperative recurrence-free rate than did those with positive expression during the 5 years of follow-up. TS expression was significantly decreased in patients who received neoadjuvant hormonal therapy. No relationship was found between the expression of TS and DPD. Patients with prostate cancer with either negative TS or DPD expression had a significantly longer postoperative disease-free rate than those with positive expression of both during the 5 years of follow-up. Conclusions: The results of the present study have shown for the first time that TS expression could be a prognostic marker for patients with prostate cancer undergoing radical prostatectomy. In addition, the combination of TS and DPD expression might also be helpful for the prediction of the prognosis of patients with prostate cancer.
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