title: Immunohistochemical dihydropyrimidine dehydrogenase expression is a good prognostic indicator for patients with Dukes' C colorectal cancer.
abstract: BACKGROUND
  Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU), which is widely used for chemotherapy in patients with advanced colorectal cancer (CRC). However, the clinical importance of tumor dihydropyrimidine dehydrogenase (DPD) expression in patients with CRC treated with 5-FU remains unclear.
  
  
  METHODS
  We investigated DPD activities in normal mucosa (N) and tumors (T) by enzyme-linked immunosorbent assay (ELISA) in 64 surgically resected patients with Dukes' C CRC who were treated orally with postoperative adjuvant FU-based chemotherapy. We also immunohistochemically investigated DPD expression in these specimens. The clinicopathological importance of DPD activity and expression was evaluated in the patients.
  
  
  RESULTS
  Positive DPD expression was detected in 28 tumors (43.8%) and tumor DPD activity significantly correlated with tumor DPD immunoreactivity (p=0.0121). Further, tumor DPD activity and immunoreactivity also correlated with lymph node metastatic status (p=0.0409). The disease-free survival rate of patients with positive-tumor DPD expression was significantly worse than that of patients with negative-tumor DPD expression (39.3% vs. 72.2%, p=0.0127). However, DPD activity in tumors or normal mucosa did not correlate with patient prognosis. Tumor DPD expression appeared to be an important poor prognostic factor in patients with Dukes' C CRC by multivariate analysis (p=0.013).
  
  
  CONCLUSIONS
  Immunohistochemical DPD expression in tumors is a useful prognostic parameter in patients with Dukes' C CRC treated with postoperative adjuvant FU-based chemotherapy.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, School of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan. kentaro@grape.med.tottori-u.ac.jp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oi
authors.forename: Masato
authors.initials: M
authors.lastname: Makino
authors.forename: Mai
authors.initials: M
authors.lastname: Ozaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takemoto
authors.forename: Nariyuki
authors.initials: N
authors.lastname: Yamane
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masahide
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kaibara
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil