title: Association between preoperative plasma levels of tissue inhibitor of metalloproteinases 1 and rectal cancer patient survival. a validation study.
abstract: The level of the tissue inhibitor of metalloproteinases 1 (TIMP-1) has previously been demonstrated to predict the survival of early stage colorectal cancer patients. The present study was undertaken to further validate plasma TIMP-1 as a prognostic marker in rectal cancer. Preoperative plasma from 352 rectal cancer patients were analysed using an immunoassay for TIMP-1. The TIMP-1 immunoassay demonstrated robustness and good reproducibility with low interassay coefficients of variation (CV). The rectal cancer patients had a mean plasma TIMP-1 level of 184 microg/l (standard deviation (SD): 70 microg/l). There were no significant differences in TIMP-1 levels between patients with Dukes' stage A, B or C disease, whereas Dukes' stage D patients had significantly increased TIMP-1 levels (P<0.0001); however, high levels of TIMP-1 were not restricted to those with advanced disease. Univariate analysis demonstrated an increasing risk of mortality with increasing TIMP-1 levels Hazard Ratio (HR)=2.9; 95% Confidence Interval (CI): 1.7-5.0; P<0.0001). Including additional covariates, multivariate analysis identified plasma TIMP-1 as an independent prognostic marker (HR=2.2; 95% CI: 1.2-4.1 (P=0.01). This study showed a highly significant and independent association between preoperative plasma TIMP-1 levels and survival in rectal cancer patients, thus confirming our previous findings. Furthermore, the TIMP-1 immunoassay proved to be stable and reproducible in this confirmatory study.
authors.affiliation: Institute for Pharmacology and Pathobiology, The Royal Danish Veterinary and Agricultural University, Ridebanevej 9, 1870 Frederiksberg C, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Holten-Andersen
authors.forename: I J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: M
authors.initials: M
authors.lastname: Nilbert
authors.forename: P O
authors.initials: PO
authors.lastname: Bendahl
authors.forename: H J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: N
authors.initials: N
authors.lastname: Brünner
authors.forename: E
authors.initials: E
authors.lastname: Fernebro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000097:blood*; D010976:Platelet Count; D011182:Postoperative Care; D011300:Preoperative Care; D011379:Prognosis; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D002272:Carcinoembryonic Antigen; D009363:Neoplasm Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1