title: Role of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA in intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil and possible predictive markers. We conducted this study to clarify if TS and DPD gene expressions are a prognostic indicator for intrahepatic cholangiocarcinoma (IHCC).
  
  
  METHODS
  The subjects of this study were 21 patients with IHCC who had undergone surgical resection. Intratumoral TS and DPD mRNA expressions were examined using the Danenberg tumor profile method and classified into two groups according to the median value of each. We then compared the clinicopathological variables, including prognosis, between the high and low expression groups.
  
  
  RESULTS
  Low DPD expression was correlated with macroscopic type, namely, mass-forming + infiltrative (P = 0.08). Postoperative survival rates in the low DPD expression group were significantly lower than those in the high DPD expression group. Multivariate analysis revealed macroscopic type to be an independent prognostic factor, whereas TS mRNA expression did not correlate with any clinicopathological variables, including prognosis.
  
  
  CONCLUSIONS
  Low DPD mRNA expression was related to macroscopic type and associated with poor prognosis. DPD mRNA expression in tumor cells is suggested to be an important regulator of malignant behavior in IHCC.
authors.affiliation: Department of Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan. ymorine@clin.med.tokushima-u.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Jun
authors.initials: J
authors.lastname: Hanaka
authors.forename: Mami
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurita
authors.forename: Hidenori
authors.initials: H
authors.lastname: Miyake
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase