Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer

Abstract

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.