title: High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase.
abstract: OBJECTIVE
  To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Kyoto University Graduate Schol of Medicine, Sakyoku, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Takehiko
authors.initials: T
authors.lastname: Segawa
authors.forename: Taizo
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamada
authors.forename: Naoko
authors.initials: N
authors.lastname: Kinukawa
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Toda
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Eijiro
authors.initials: E
authors.lastname: Nakamura
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase