Prognostic effects of dihydropyrimidine dehydrogenase in advanced colorectal cancer after surgery: immunohistochemistry using a new monoclonal antibody.
BACKGROUND
The response rate of 5-FU and its clearance are due to the activity of dihydropyrimidine dehydrogenase (DPD), which is the first and rate-limiting enzyme for the catabolism of 5-FU. Although several studies have evaluated the relationship between DPD expression and chemosensitivity to 5-FU in patients with colorectal cancer (CRC), only a few studies on DPD expression and clinicopathological features have been conducted using immunohistochemical staining since a monoclonal antibody for DPD has not been established. Now, a new monoclonal antibody (2H9-1b) for human DPD is available.


METHODS
This study included 100 patients whose CRCs were classified into stage II to IV and completely resected surgically in our institute. DPD expression in CRC was evaluated by using immunohistochemical staining with 2H9-1b. The relationship between DPD expression and clinicopathological variables that might have affected the patients' prognosis were evaluated. Survival curves were calculated with the Kaplan-Meier method and differences were evaluated with the log-rank test. The Cox proportional hazards model was used in the univariate and multivariate survival analyses.


RESULTS
DPD expression showed a positive correlation with advances in lymphatic invasion (p = 0.066), venous invasion (p = 0.033) and cancer stage (p = 0.033). The patients' survival rates after surgery were significantly (p = 0.018) higher in those DPD-negative than in those DPD-positive. The overall estimated hazard ratio for death in patients with DPD expression was 4.79 according to univariate analysis (p = 0.033). Multivariate analysis showed that DPD expression tended to be a prognostic factor less potent than other variables such as lymph node metastasis and venous invasion.


CONCLUSIONS
With a new sensitive monoclonal antibody to human DPD, the present results indicated that DPD expression is associated with CRC progression and invasion, and closely correlated with poor prognosis in postoperative CRC patients. Moreover, DPD expression is a prognostic factor in CRC patients.
Tokunaga
Yukihiko
Y
Department of Surgery, Maizuru Municipal Hospital, Kyoto, Japan.
Nakagami
Mikio
M
Tokuka
Atsuo
A
Ohsumi
Kiyoshi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000276:immunology; D011379:Prognosis; D016016:Proportional Hazards Models
D000911:Antibodies, Monoclonal; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP)