High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase.
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.
Inoue
Takahiro
T
Department of Urology, Kyoto University Graduate Schol of Medicine, Sakyoku, Kyoto, Japan.
Segawa
Takehiko
T
Shiraishi
Taizo
T
Yamada
Tomomi
T
Kinukawa
Naoko
N
Yoshida
Toru
T
Toda
Yoshinobu
Y
Shimizu
Yosuke
Y
Nakamura
Eijiro
E
Kinoshita
Hidefumi
H
Kamoto
Toshiyuki
T
Ogawa
Osamu
O
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*
D018931:Antineoplastic Agents, Hormonal; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase