title: Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: a prospective validation study.
abstract: BACKGROUND
  Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC.
  
  
  METHODS
  During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms.
  
  
  RESULTS
  High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels.
  
  
  CONCLUSIONS
  This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.
authors.affiliation: Department of Surgery, Uppsala University, 75185 Uppsala, Sweden. helgi.birgisson@surgsci.uu.se
authors.forename: Helgi
authors.initials: H
authors.lastname: Birgisson
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D009363:Neoplasm Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1