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Prognostic impact of dihydropyrimidine dehydrogenase expression on pancreatic adenocarcinoma patients treated with S-1-based adjuvant chemotherapy after surgical resection.

AbstractBACKGROUND AND OBJECTIVES:
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.
AuthorsNaru Kondo, Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Akira Nakashima, Hiroki Ohge, Taijiro Sueda
JournalJournal of surgical oncology (J Surg Oncol) Vol. 104 Issue 2 Pg. 146-54 (Aug 01 2011) ISSN: 1096-9098 [Electronic] United States
PMID21538357 (Publication Type: Journal Article)
CopyrightCopyright © 2011 Wiley-Liss, Inc.
Chemical References
  • Antineoplastic Agents
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Orotate Phosphoribosyltransferase
Topics
  • Adenocarcinoma (drug therapy, metabolism, surgery)
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (therapeutic use)
  • Chemotherapy, Adjuvant
  • Dihydrouracil Dehydrogenase (NADP) (biosynthesis)
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Orotate Phosphoribosyltransferase (biosynthesis)
  • Oxonic Acid (therapeutic use)
  • Pancreatectomy
  • Pancreatic Neoplasms (drug therapy, metabolism, surgery)
  • Prognosis
  • Tegafur (therapeutic use)
  • Thymidylate Synthase (biosynthesis)

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