Immunohistochemical dihydropyrimidine dehydrogenase expression is a good prognostic indicator for patients with Dukes' C colorectal cancer.
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.
Oi
Kentaro
K
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
Makino
Masato
M
Ozaki
Mai
M
Takemoto
Hiroki
H
Yamane
Nariyuki
N
Nakamura
Seiichi
S
Ikeguchi
Masahide
M
Kaibara
Nobuaki
N
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
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil