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


METHODS
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.
Holten-Andersen
Mads N
MN
The Finsen Laboratory, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark. mads@finsenlab.dk
Christensen
Ib Jarle
IJ
Nielsen
Hans Jørgen
HJ
Stephens
Ross W
RW
Jensen
Vibeke
V
Nielsen
Ole Haagen
OH
Sørensen
Steen
S
Overgaard
Jens
J
Lilja
Hans
H
Harris
Adrian
A
Murphy
Gillian
G
Brünner
Nils
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001782:Blood Donors; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1