Increased levels of tissue inhibitor of metalloproteinase-1 in human hepatocellular carcinoma

Background: Invasion and metastasis of hepatocellular carcinoma (HCC) are regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, the role of TIMPs in these processes is not clear. Aim: To examine the potential involvement of TIMP-1 in HCC and the association between TIMP-1 and clinical outcome of patients with HCC. Methods: The study included 91 patients who underwent surgical removal of HCC. TIMP-1 concentrations in the supernatant of tissue homogenates of HCC and non-neoplastic liver were measured by enzyme immunoassay. The relationships between TIMP-1 concentration and various clinicopathological features and recurrence of HCC after surgical operation were examined. Results: The mean level of TIMP-1 in HCC (486 ± 610ng/mg protein, ± SD) was significantly higher than in the non-neoplastic liver (75 ± 69, P<0.0001). The median level of TIMP-1 in poorly differentiated HCCs (701 ng/mg protein) was significantly higher than in well- (80) and moderately (172) differentiated HCCs (P = 0.0047 and P = 0.0082, respectively). TIMP-1 level in liver cirrhosis was higher than in chronic hepatitis (P = 0.0015). TIMP-1 levels in HCC did not influence the recurrence rate of HCC. Conclusions: TIMP-1 concentration in HCC was higher than in non-neoplastic liver and correlated with the differentiation grade of HCCs. However, tissue TIMP-1 concentration does not seem to be an important determinant of HCC recurrence.