title: A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer.
abstract: BACKGROUND
  Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC).
  
  
  METHODS
  A total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively planned molecular substudy, and of them, 59% had rectal cancer and about 90% received adjuvant chemotherapy (either systemically or randomly allocated to intraportal 5-fluorouracil infusion or both). TS and p53 status were determined, blinded to any clinical data, by immunohistochemistry using a validated polyclonal antibody or the DO-7 clone, respectively, and their relationships with overall survival were examined.
  
  
  RESULTS
  High TS expression was observed in 58% and overexpression of p53 in 60% of tumours. TS expression correlated with tumour stage, and p53 overexpression, with rectal cancers. There was no evidence that either marker was significantly associated with survival by either univariate (TS hazard ratio (HR) = 0.94, 95% CI 0.76-1.18 and P = 0.6 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.9) or multivariate analyses (TS HR = 0.99, 95% CI 0.79-1.25 and P = 0.9 and p53 HR = 0.98, 95% CI 0.78-1.23 and P = 0.8).
  
  
  CONCLUSIONS
  Neither TS nor p53 expression has significant prognostic value in the adjuvant setting of CRC.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. sanjay.popat@icr.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Popat
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.forename: N
authors.initials: N
authors.lastname: Hearle
authors.forename: I
authors.initials: I
authors.lastname: Chandler
authors.forename: Y
authors.initials: Y
authors.lastname: Shao
authors.forename: W
authors.initials: W
authors.lastname: Aherne
authors.forename: Rs
authors.initials: R
authors.lastname: Houlston
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013940:Thymidylate Synthase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase; D005472:Fluorouracil