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High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase.

Inoue T, Segawa T, Shiraishi T, Yamada T, Kinukawa N, Yoshida T, Toda Y, Shimizu Y, Nakamura E, Kinoshita H, Kamoto T, Ogawa O

Department of Urology, Kyoto University Graduate Schol of Medicine, Sakyoku, Kyoto, Japan.

OBJECTIVE: To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue. MATERIALS AND METHODS: Tissue from 79 patients with localized prostate cancer was used. Thymidylate synthase and dihydropyrimidine dehydrogenase expression were determined semiquantitatively by immunohistochemistry. RESULTS: Thymidylate synthase and dihydropyrimidine dehydrogenase immunostaining grades of benign tissue were significantly higher than those of cancer tissue (both P < 0.01). Cancer tissue with a primary Gleason grade of > or = 4 expressed a higher thymidylate synthase staining grade than those with a primary Gleason grade of <4 (P < 0.01). Cancer tissue spots from patients treated with neoadjuvant therapy revealed significantly higher thymidylate synthase and dihydropyrimidine dehydrogenase grades than those with no neoadjuvant therapy (P < 0.01). CONCLUSION: High thymidylate synthase expression in localized prostate cancer might reflect an aggressive status. High expression in high-grade prostate cancers and prostate cancers after hormonal therapy suggest that thymidylate synthase could be a new therapeutic target for advanced prostate cancer.

Published 11 July 2006 in BJU Int, 98(1): 197-200.
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