Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer

Mads N Holten-Andersen, Ib Jarle Christensen, Hans Jørgen Nielsen, Ross W Stephens, Vibeke Jensen, Ole Haagen Nielsen, Steen Sørensen, Jens Overgaard, Hans Lilja, Adrian Harris, Gillian Murphy, Nils Brünner

Abstract

PURPOSE: The purpose of this study was to measure total levels of tissue inhibitor of metalloproteinases (TIMP-1) by ELISA in plasma from blood donors, patients with inflammatory bowel disease (IBD), and patients with cancer and to correlate the results to patient diagnosis.

EXPERIMENTAL DESIGN: Total TIMP-1 plasma levels were measured by ELISA in blood samples from two different blood donor populations from IBD patients, and preoperative samples from patients with primary colon cancer (CC), rectal cancer (RC), or breast cancer.

RESULTS: There were no significant differences in plasma TIMP-1 levels between healthy donors and IBD or breast cancer patients, whereas patients with CC or RC had significantly elevated TIMP-1 levels. Total TIMP-1 levels identified patients with CC with a sensitivity of 63% at 98% specificity, patients with early CC (Dukes' A+B) with a sensitivity of 56% at 98% specificity, and patients with right-sided CC with a sensitivity of 72% at 98% specificity. Combining carcinoembryonic antigen and TIMP-1 measurements increased the sensitivities obtained from TIMP-1 measurements alone.

CONCLUSIONS: TIMP-1 was significantly elevated in plasma from CC and RC patients, including those with early-stage disease. Sensitivity and specificity were both sufficiently high to consider TIMP-1 as a marker for the early identification of CC patients, in particular, those with right-sided CC.

Original languageEnglish
JournalClinical Cancer Research
Volume8
Issue number1
Pages (from-to)156-64
Number of pages9
ISSN1078-0432
Publication statusPublished - Jan 2002

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/blood
  • Blood Donors
  • Breast Neoplasms/enzymology
  • Colonic Neoplasms/enzymology
  • Female
  • Humans
  • Inflammatory Bowel Diseases/enzymology
  • Male
  • Middle Aged
  • Rectal Neoplasms/enzymology
  • Reference Values
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-1/blood

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