ELEVATED PLASMA-LEVELS OF MATRIX METALLOPROTEINASE-9 (92-KD TYPE-IV COLLAGENASE GELATINASE-B) IN HEPATOCELLULAR-CARCINOMA

Background, Matrix metalloproteinase 9 (MMP-9), a 92-kd gelatinase/typ e IV collagenase, has been implicated as playing an important role in cancer invasion and metastasis. A previous study showed that serum typ e IV collagenase activity correlated with metastasis by hepatocellular carcinoma (HCC), The aims of this study were to determine the plasma levels of immunoreactive MMP-9 in patients with HCC and to compare the levels with the clinical features including vascular invasion, Patien ts and Methods, This study included 100 patients with HCC, 21 patients with chronic hepatitis (CH), 24 patients with Liver cirrhosis (LC), a nd 138 healthy control subjects, Plasma MMP-9 levels were measured wit h a specific one-step sandwich enzyme immunoassay, Results, Plasma MMP -9 levels in HCC (62 [33 to 130 ng/mL] median [25%, 75%], 13 to 660 ng /mL, minimum, maximum) were significantly elevated compared with those in normal controls (36 [25 to 45], range, 2.8-70 ng/mL), in CH (28 [1 8 to 30], 13 to 66 ng/mL) and in LC (35 [26 to 58], 16 to 86 ng/mL) (P <.0000001; P =.0000003; and P = .00205, respectively), When the cut-o ff level was defined as 60 ng/mL from a receiver operating characteris tic curve, plasma MMP-9 concentrations had a sensitivity of 53% and a specificity of 89% for the detection of HCC from CB and LC, The levels were significantly higher in HCC patients with macroscopic portal ven ous invasion (79 [36 to 160], 15-660 ng/mL) than those without the inv asion (44 [27 to 80], 13 to 210 ng/mL) (P =.00726), Plasma MMP-9 level s in patients with HCC were not correlated with tumor number, size, vo lume, or serum cu-fetoprotein levels, Conclusions, The present data su ggest that plasma MMP-9 levels can be a candidate for a novel marker f or HCC, The levels appear to reflect its potential and ongoing activit y of vascular invasion, A long-term follow-up of the patients will be necessary to determine whether increased plasma MMP-9 levels are predi ctive of more invasive and metastatic HCC.