BACKGROUND:

Matrix metalloproteinase 9 (MMP-9), a 92-kd gelatinase/type IV collagenase, has been implicated as playing an important role in cancer invasion and metastasis. A previous study showed that serum type 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.

PATIENTS AND METHODS:

This study included 100 patients with HCC, 21 patients with chronic hepatitis (CH), 24 patients with liver cirrhosis (LC), and 138 healthy control subjects. Plasma MMP-9 levels were measured with 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 [18 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-off level was defined as 60 ng/mL from a receiver operating characteristic curve, plasma MMP-9 concentrations had a sensitivity of 53% and a specificity of 89% for the detection of HCC from CH and LC. The levels were significantly higher in HCC patients with macroscopic portal venous invasion (79 [36 to 160], 15-660 ng/mL) than those without the invasion (44 [27 to 80], 13 to 210 ng/mL) (P = .00726). Plasma MMP-9 levels in patients with HCC were not correlated with tumor number, size, volume, or serum alpha-fetoprotein levels.

CONCLUSIONS:

The present data suggest that plasma MMP-9 levels can be a candidate for a novel marker for HCC. The levels appear to reflect its potential and ongoing activity of vascular invasion. A long-term follow-up of the patients will be necessary to determine whether increased plasma MMP-9 levels are predictive of more invasive and metastatic HCC.