title: Prognostic impact of dihydropyrimidine dehydrogenase expression on pancreatic adenocarcinoma patients treated with S-1-based adjuvant chemotherapy after surgical resection.
abstract: OBJECTIVE
  The aim of this study is to investigate the prognostic value of intratumoral expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in patients treated with S-1-based chemotherapy after surgical resection for pancreatic adenocarcinoma.
  
  
  METHODS
  Intratumoral TS, DPD, and OPRT expression was investigated in 106 patients with resected pancreatic adenocarcinoma by immunohistochemistry. Associations between clinicopathological factors, including intratumoral TS, DPD, and OPRT expression, and survival were evaluated by univariate and multivariate analyses.
  
  
  RESULTS
  Of 106 patients, 72 had received S-1-based adjuvant chemotherapy (S-1(+) group), and 34 had not (S-1(-) group). High TS, DPD, and OPRT expression was observed in 64%, 37%, and 66% of patients, respectively. Among S-1(+) group patients, survival was significantly better for patients with low DPD expression than for patients with high DPD expression (P = 0.022). Intratumoral DPD expression was the only independent prognostic factor for patients treated with S-1-based adjuvant chemotherapy by multivariate analysis (P = 0.037). Intratumoral TS and OPRT expression did not appear to influence survival.
  
  
  CONCLUSIONS
  Intratumoral DPD expression may be a relevant predictive marker of survival benefit associated with S-1-based adjuvant chemotherapy for pancreatic adenocarcinoma.
authors.affiliation: Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. k-naru@par.odn.ne.jp
authors.forename: Naru
authors.initials: N
authors.lastname: Kondo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Uemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sudo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Nakashima
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis; D010094:Oxonic Acid / Q000627:therapeutic use*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D011379:Prognosis; D005641:Tegafur / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase