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

J Surg Oncol. 2011 Aug 1;104(2):146-54. doi: 10.1002/jso.21955. Epub 2011 Apr 27.

Abstract

Background 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.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / 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
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Tegafur / therapeutic use*
  • Thymidylate Synthase / biosynthesis

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Orotate Phosphoribosyltransferase