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Total Levels of Tissue Inhibitor of Metalloproteinases 1 in Plasma Yield High Diagnostic Sensitivity and Specificity in Patients with Colon Cancer¹

The Finsen Laboratory, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark [M. N. H-A., I. J. C., R. W. S., V. J., N. B.]; Department of Surgical Gastroenterology, Hvidovre University Hospital, 2650 Hvidovre, Denmark [H. J. N.]; Department of Gastroenterology C, Herlev University Hospital, 2730 Herlev, Denmark [O. H. N.]; Department of Clinical Biochemistry, Hvidovre University Hospital, 2650 Hvidovre, Denmark [S. S.]; Department of Experimental Clinical Oncology, Århus Kommune Hospital, 8000 Århus, Denmark [J. O.]; Department of Laboratory Medicine, Division of Clinical Chemistry, University Hospital of Lund, SE 205 02 Lund, Sweden [H. L.]; Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS United Kingdom [A. H.]; and School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ United Kingdom [G. M.]

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.

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