The activity of matrix metalloproteinases
(MMPs) in degrading extracellular matrix is controlled
by activation of pro-enzymes and inhibition of MMP
tissue inhibitors (TIMPs).
To assess proteolytic cascade imbalance in
malignancy progression, the enzymatic activity of
MMP2 and MMP9 and the expression and serum level
of their inhibitors, TIMP2 and TIMP1 respectively, was
evaluated in selected patients with high-risk soft tissue
sarcoma (STS). Gelatinase activity and inhibitor
expression was evaluated on 69 biopsies by zymography
and immunohistochemistry. TIMP1 and TIMP2 serum
concentration was tested in 53 STS patients and in 56
controls using a sandwich enzyme immunoassay.
Clinical and biological variables were related to
clinical outcome of the patients.
A significant gelatinolytic activity was seen in a high
percentage of STS. TIMP expression was weak or
negative in the majority of samples. The difference
between disease-free (p=0.001) and overall survival
(p=0.007) curves based on TIMP2 immunoreactivity
was statistically significant. TIMP plasma concentration
of 53 STS revealed significantly lower levels compared
to those of 56 controls (p=0.0001).
In conclusion, low levels of negative regulators of
proteolysis may be related to tumor biological
aggressiveness and used to select patients with poor
prognosis to improve cure