title: A novel prognostic index in colorectal cancer defined by serum carcinoembryonic antigen and plasma tissue inhibitor of metalloproteinases-1.
abstract: OBJECTIVE
  The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue inhibitor of metalloproteinases (TIMP)-1 as a prognostic index in patients with primary, curatively resected CRC.
  
  
  METHODS
  Blood samples were collected before surgery from 422 patients with CRC stage I-III (Dukes' stage A-C). CEA was determined in serum by a routine analysis and TIMP-1 was determined in plasma using a validated in-house enzyme-linked immunosorbent assay. Disease-free survival (DFS) was registered and its associations with serum CEA and plasma TIMP-1 levels were studied using a Cox multivariate model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for DFS were calculated.
  
  
  RESULTS
  An event was recorded in 186 patients: 75 had local recurrence, 75 had distant metastases, 28 had both local recurrence and distant metastases, and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale, serum CEA and plasma TIMP-1 were statistically significant in a multivariate analysis with HR = 1.1 (95% CI 1.0-1.2) and HR = 1.5 (95% CI 1.1-2.0), respectively. The two serological markers could be combined to form a prognostic index adjusted for baseline variables. This index showed a 51% increase in HR for a given CEA level if the TIMP-1 level was doubled.
  
  
  CONCLUSIONS
  Preoperative serum CEA and plasma TIMP-1 levels are independent predictors of DFS in patients with primary resectable CRC. In combination these two proteins could form an index for the assessment of risk of disease recurrence in early-stage CRC.
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. h.j.nielsen@ofir.dk
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1