Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer.
A kinetic enzyme-linked immunosorbent assay (ELISA) for plasma tissue inhibitor of metalloproteinase (TIMP)-1 was developed in order to examine the potential diagnostic and prognostic value of TIMP-1 measurements in cancer patients. The ELISA enabled specific detection of total TIMP-1 in EDTA, citrate and heparin plasma. The assay was rigorously tested and requirements of sensitivity, specificity, stability and good recovery were fulfilled. TIMP-1 levels measured in citrate plasma (mean 69.2+/-13.1 microg I(-1)) correlated with TIMP-1 measured in EDTA plasma (mean 73.5+/-14.2 microg I(-1)) from the same individuals in a set of 100 healthy blood donors (Spearman's rho = 0.62, P< 0.0001). The mean level of TIMP-1 in EDTA plasma from 143 patients with Dukes' stage D colorectal cancer was 240+/-145 microg I(-1) and a Mann-Whitney test demonstrated a highly significant difference between TIMP-1 levels in healthy blood donors and colorectal cancer patients (P < 0.0001). Similar findings were obtained for 19 patients with advanced breast cancer (mean 292+/-331 microg I(-1)). The results show that TIMP-1 is readily measured in plasma samples by ELISA and that increased levels of TIMP-1 are found in patients with advanced cancer. It is proposed that plasma measurements of TIMP-1 may have value in the management of cancer patients.
The Finsen Laboratory, Copenhagen University Hospital, Denmark.
M N
MN
Holten-Andersen
G
G
Murphy
H J
HJ
Nielsen
A N
AN
Pedersen
I J
IJ
Christensen
G
G
Høyer-Hansen
N
N
Brünner
R W
RW
Stephens
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001782:Blood Donors; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D002951:Citrates / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D004492:Edetic Acid / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000097:blood / Q000302:isolation & purification; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000235:genetics
D002951:Citrates; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D004492:Edetic Acid