Abstract 1738: Significance of thymidylate synthase expression in prostate cancer

Abstract Introduction : Thymidylate synthase (TS) is an important rate-limiting enzyme in the pathway of de novo DNA synthesis. Several reports demonstrated that TS expression was up-regulated in various cancers. 5-fluorouracil (5-FU) is an anti-cancer agent used clinically against a variety of cancers including prostate cancer. TS is a target enzyme for 5-FU. 5-FU inhibits DNA synthesis by binding TS and folic acid. We then investigated the expression of TS in prostate cancer and investigated its prognostic significance. Materials and Methods : Total 100 prostate cancer tissue specimens were obtained from patients who underwent radical prostatectomy for prostate cancer. Fifty-two patients did not received neoadjuvant hormonal therapy, and the rest 48 patients received neoadjuvant hormonal therapy. We examined prostate cancer tissues and normal prostate tissues for TS expression by immunohistochemistry. TS expression was regarded as positive, when more than 25% cells showed positive staining. If less than 25% were positive staining, TS expression was regarded as negative. Results : TS in prostate cancer tissues expressed at higher levels in patients without neoadjuvant hormonal therapy, compared with normal prostate tissues. TS expression was positive in approximately 70% prostate cancer tissues. In contrast, TS expression was observed in about 10% normal prostate tissues. The positive rate of TS expression in Stage T3 prostate cancer was higher than that in Stage T2 prostate cancer. In addition, the rate of positive TS expression in Gleason score 7 or greater prostate cancer was higher than that in Gleason score less than 7 prostate cancer. Patients with prostate cancer with negative TS expression without neoadjuvant hormonal therapy had a longer postoperative recurrence-free rate than those with positive expression in the 5 year follow-up. The rate of positive TS expression in prostate cancer tissues was significantly down-regulated in patients who received neoadjuvant hormonal therapy, compared with no neoadjuvant hormonal therapy. Especially, the rate of positive TS expression in stage T2 prostate cancer tissues was decreased by neoadjuvant hormonal therapy. Conclusions : The present study has demonstrated for the first time that TS expression may be a prognostic parameter for prostate cancer patients undergoing radical prostatectomy, and that TS may be a molecular therapeutic target for prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1738.