Thymidylate synthase and dihydropyrimidine dehydrogenase expressions in gallbladder cancer.
BACKGROUND
Although 5-Fluorouracil (5-FU) is widely used in chemotherapeutic treatment for gallbladder cancer, there is little evidence of its effectiveness. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are the major determinants of individual sensitivity to 5-FU, and the impact of TS and DPD expression on prognosis and 5-FU efficacy has been studied in gastrointestinal carcinomas.


METHODS
TS and DPD enzymatic activities in frozen samples of 7 gallbladder cancer tissues and immunohistochemical TS and DPD protein expressions in 53 resected gallbladder cancers were evaluated.


RESULTS
The DPD activity of gallbladder cancers was significantly higher than that of gastric and colon cancers (p=0.041). TS and DPD protein expressions increased in pT2 and pT3 cases compared to those in pT1 cases, and cases both with high TS and DPD expressions had a worse prognosis than both low TS and DPD expressions. However, TS and DPD expressions were not independent prognostic factors.


CONCLUSIONS
TS and DPD protein expressions in gallbladder cancers were frequently high in pT2 and pT3 gallbladder cancers and control of high TS or DPD levels may be important for advanced gallbladder cancer therapy.
Ajiki
Tetsuo
T
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kobe, Japan. ajiki@med.kobe-u.ac.jp
Hirata
Kenro
K
Okazaki
Taro
T
Horiuchi
Hideki
H
Fujita
Tsunenori
T
Habara
Kazuto
K
Kamigaki
Takashi
T
Suzuki
Yasuyuki
Y
Kuroda
Yoshikazu
Y
D000368:Aged; D003110:Colonic Neoplasms / Q000201:enzymology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D005260:Female; D005706:Gallbladder Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000096:biosynthesis*
D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase