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.

PATIENTS AND 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: Helgi Birgisson, Hans J Nielsen, Ib Jarle Christensen, Bengt Glimelius, Nils Brünner
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 46 Issue 18 Pg. 3323-31 (Dec 2010) ISSN: 1879-0852 [Electronic] England
• PMID: 20619633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Carcinoembryonic Antigen
• Neoplasm Proteins
• Tissue Inhibitor of Metalloproteinase-1

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood)
• Carcinoembryonic Antigen (blood)
• Colorectal Neoplasms (blood, mortality, surgery)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)
• Preoperative Care
• Prognosis
• Prospective Studies
• Tissue Inhibitor of Metalloproteinase-1 (blood)