title: Tumor dihydropyrimidine dehydrogenase in stage II and III colorectal cancer: low level expression is a beneficial marker in oral-adjuvant chemotherapy, but is also a predictor for poor prognosis in patients treated with curative surgery alone.
abstract: The aim of this study was to evaluate the prognostic significance of tumor dihydropyrimidine dehydroganase (DPD) in curatively resected colorectal cancer patients who received or did not receive oral 5-FU based-adjuvant chemotherapy. Among 182 patients with stage II-III colorectal cancers, 89 patients (adjuvant chemotherapy group) received oral 5-FU based-adjuvant chemotherapy, and 93 patients (surgery alone group) did not receive 5-FU. DPD expressions in the tumors and in the normal colonic mucosa were measured by enzyme-linked immunosorbent assays. The mean DPD expression of the tumors was significantly lower than that of the normal mucosa (54.4 +/- 40.4 versus 72.3 +/- 23.3 Unit/mg protein, P < 0.01). For survival analyses, we designated the cut-off value of tumor DPD as its median value (46.3). In the adjuvant chemotherapy group, high tumor DPD levels were associated with poor survival (HR, 5.24; P = 0.03). In the surgery alone group, high tumor DPD levels were associated with better survival (HR, 0.32; P = 0.02). In conclusion, tumor DPD level is an efficacious marker in oral 5-FU based-adjuvant chemotherapy for colorectal cancer; however, low tumor DPD predicts reduced survival in patients treated with curative surgery alone.
authors.affiliation: Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 852-8501, Japan. bannv@bolero.plala.or.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Terumitsu
authors.initials: T
authors.lastname: Sawai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeshita
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagoe
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Hidaka
authors.lastname: Atsushi Nanashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Yasutake
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tagawa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil