title: Thymidylate synthase, topoisomerase-1 and microsatellite instability: relationship with outcome in mucinous colorectal cancer treated with fluorouracil.
abstract: BACKGROUND
  Mucinous colorectal cancer (CRC) exhibits distinct clinical and pathological features, including poorer response to fluorouracil (FU) compared with non-mucinous tumours.
  
  
  METHODS
  We compared the expression of thymidylate synthase (TYMS) and topoisomerase-1 (TOPO1) and DNA microsatellite instability (MSI) in 87 patients (35 mucinous and 52 non-mucinous CRCs) enrolled in three randomized trials, evaluating infused FU as first-line treatment.
  
  
  RESULTS
  Mucinous CRCs more frequently had high TOPO1 expression than did non-mucinous tumors (41% vs. 15%, p=0.028). The median overall survival was 14.2 months for patients with mucinous CRC with low TOPO1 expression compared with 9.7 months for high TOPO1-expressing cases (p=0.016). After adjusting for confounding variables, low TOPO1 expression was statistically favourably associated with overall survival (hazard ratio=0.55; p=0.041).
  
  
  CONCLUSIONS
  Our data suggest the TOPO1 expression levels to be a prognostic marker in patients with mucinous CRC treated with FU. If further verified, these data might redefine therapeutic strategies by identifying categories of patients with a worse prognosis.
authors.affiliation: Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy. francescanegri2@hotmail.com.
authors.forename: Francesca V
authors.initials: FV
authors.lastname: Negri
authors.forename: Cinzia
authors.initials: C
authors.lastname: Azzoni
authors.forename: Lorena
authors.initials: L
authors.lastname: Bottarelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Campanini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Andrew
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Silini
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D005472:Fluorouracil
keywords: 5-fluorouracil; Mucinous colorectal cancer; microsatellite instability; thymidylate synthase; topoisomerase-1