title: Correlation between clinical pathologic factors and activity of 5-FU-metabolizing enzymes in colorectal cancer.
abstract: BACKGROUND
  Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD), and thymidylate synthase (TS) are initial key enzymes in the 5-fluorouracil (5-FU) metabolic pathway. The expression levels and activities of these three enzymes play important roles in the response of cancer patients to 5-FU-based chemotherapy.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the relationship between the activities of 5-FU metabolic enzymes and clinicopathologic factors in colorectal cancer.
  
  
  METHODS
  We measured the activities of OPRT, DPD, and TS in colorectal cancer tissues. We also investigated the correlations between the activities of these three enzymes and clinicopathologic factors (histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, and vascular invasion). We examined 100 patients with surgically resected colorectal cancer.
  
  
  RESULTS
  Poorly differentiated adenocarcinoma showed significantly higher DPD activities than did moderately differentiated or well-differentiated adenocarcinoma. In patients with lymph-node metastasis, OPRT activity was significantly lower than in patients without lymph-node metastasis. No significant relation was found between TS activity and histological type, depth of tumor invasion, extent of lymph node metastasis, Dukes' stage, lymphatic invasion, or vascular invasion.
  
  
  CONCLUSIONS
  The response to 5-FU may be poor in patients with lymph-node metastasis, because of low OPRT activity, and in patients with poorly differentiated adenocarcinoma, because of high DPD activity.
authors: Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School, Japan. y-tak@nms.ac.jp
authors: Takeshi
authors: T
authors: Yamada
authors: Noritake
authors: N
authors: Tanaka
authors: Kimiyoshi
authors: K
authors: Yokoi
authors: Tomoko
authors: T
authors: Seya
authors: Yoshikazu
authors: Y
authors: Kanazawa
authors: Michihiro
authors: M
authors: Koizumi
authors: Yoshiharu
authors: Y
authors: Ohaki
authors: Takashi
authors: T
authors: Tajiri
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil