title: Prognostic significance of thymidylate synthase in patients with metastatic colorectal cancer who receive protracted venous infusions of 5-fluorouracil.
abstract: BACKGROUND
  This study was conducted to evaluate the prognostic significance of thymidylate synthase (TS) expression in the tumor tissue of patients with metastatic colorectal cancer (CRC) who received protracted venous infusions of 5-fluorouracil (5-FU).
  
  
  METHODS
  We retrospectively analyzed the prognostic value of TS expression as compared with other clinical prognostic factors in 57 patients with metastatic CRC.
  
  
  RESULTS
  On univariate analysis, survival was significantly related to TS expression (low vs high; P = 0.0015), alkaline phosphatase (ALP) level (<300 vs > or =300 IU/l; P = 0.0037), performance status (0 or 1 vs 2 or 3; P = 0.0073), and white blood cell count (<10,000/mm3 vs > or =10,000/mm3; P = 0.0001), with number of metastatic sites (1 vs > or =2; P = 0.06) approaching significance. On multivariate analysis, survival was significantly related to TS expression (hazard ratio [HR], 2.97) and ALP level (HR, 2.26).
  
  
  CONCLUSIONS
  In patients with metastatic CRC who received protracted venous infusions of 5-FU, TS expression was related to survival independently of other established clinical prognostic factors.
authors.affiliation: Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Hosokawa
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Hideko
authors.initials: H
authors.lastname: Morita
authors.forename: Mari
authors.initials: M
authors.lastname: Araake
authors.forename: Hiromi
authors.initials: H
authors.lastname: Orita
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000096:biosynthesis*
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D005472:Fluorouracil