Tumor dihydropyrimidine dehydrogenase expression is a useful marker in adjuvant therapy with oral fluoropyrimidines after curative resection of colorectal cancer.
OBJECTIVE
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluoropyrimidine (5-FU) catabolism. We examined whether tumor DPD expression is an effective marker in adjuvant therapy with oral fluoropyrimidines after curative resection of colorectal cancer.


METHODS
We studied 89 patients with stage II-III colorectal cancers who had undergone curative resections and received oral 5-FU-based adjuvant chemotherapy. The levels of DPD expression in tumor and normal colonic mucosa were measured by an enzyme-linked immunosorbent assay. In 53 tumor samples, DPD enzymatic activity was also analyzed in order to evaluate the relationship between DPD expression and enzymatic activity.


RESULTS
DPD expression significantly correlated with DPD enzymatic activity in these 53 tumors ( r=0.56; P<0.001). DPD expression in the tumors was significantly lower than in normal mucosa (47.1+/-30.8 and 56.4+/-18.5 U/mg protein, respectively; P<0.05). We designated the cut-off value of tumor DPD as its median value (46.0 U/mg protein). Patients with low DPD expression had longer disease-free intervals than those with high DPD expression according to univariate analysis ( P=0.026). In a multivariate analysis, low DPD expression was significantly and independently associated with better survival.


CONCLUSIONS
Tumor DPD expression is a useful marker for use with adjuvant chemotherapy with oral fluoropyrimidines after curative resection of colorectal cancer.
Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. bannv@bolero.plala.or.jp
Takashi
T
Tsuji
Terumitsu
T
Sawai
Hiroaki
H
Takeshita
Tohru
T
Nakagoe
Shigekazu
S
Hidaka
Hiroyuki
H
Yamaguchi
Toru
T
Yasutake
Takeshi
T
Nagayasu
Yutaka
Y
Tagawa
D000284:Administration, Oral; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007413:Intestinal Mucosa; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil