Mn. Holten-andersen et al., High preoperative plasma tissue inhibitor of metalloproteinase-1 levels are associated with short survival of patients with colorectal cancer, CLIN CANC R, 6(11), 2000, pp. 4292-4299
The objective of the present study was to measure preoperative plasma tissu
e inhibitor of metalloproteinase (TIMP)-1 levels in colorectal cancer patie
nts and relate these values to clinical and biochemical patient characteris
tics. TIMP-1 levels were determined by ELISA in EDTA plasma samples collect
ed preoperatively from 588 colorectal cancer patients. Plasma TIMP-1 levels
were distributed with a median value of 141.1 mug/liter (range, 53.7-788.7
mug/liter). Whereas no significant differences were found in the median pl
asma TIMP-1 levels among patients with Dukes' stage A, B, and C disease, pa
tients with Dukes' stage D disease had significantly higher plasma TIMP-1 l
evels (P < 0.0001); however, high plasma TIMP-1 levels were not restricted
to advanced disease. A relatively weak correlation between plasma TIMP-1 le
vel and age was found (r = 0.35; P < 0.0001), There was no significant diff
erence in TIMP-1 levels between males and females (P = 0.97), Univariate an
alysis demonstrated an increasing risk of mortality with increasing TIMP-1
levels [scored as the log,(TIMP-1); hazard ratio 33; 95% confidence interva
l, 2.6-4.2; P < 0.0001], Including covariates (Dukes' stage, primary tumor
location, gender, age, plasminogen activator inhibitor type 1, and soluble
urokinase plasminogen activator receptor) in a multivariate analysis, TIMP-
1 was retained in the final model (hazard ratio = 2.5; 95% confidence inter
val, 1.7-3.7; P < 0.0001), This study showed a highly significant associati
on between preoperative plasma TIMP-1 levels and survival in colorectal can
ter patients, with higher plasma TIMP-1 levels being associated with poor o
utcome, independent of clinical parameters including Dukes' stage, plasma T
IMP-1 levels were found to strongly predict prognosis of colorectal ranter
patients. Additional studies are needed to validate the clinical usefulness
of plasma TIMP-1 measurements.