OVEREXPRESSION OF MATRIX METALLOPROTEINASE-9 GENE IN HEPATOCELLULAR-CARCINOMA WITH INVASIVE POTENTIAL

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incide nce of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to in vestigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) ill particular, MMP-2 an d MMP-9 and the corresponding tissue inhibitor of metalloproteinase (T IMP-2 and TIMP-1), because these enzymes participate in the degradatio n of the extracellular matrix including the basement membrane, Tumorou s and adjacent nontumorous liver samples were obtained from 23 HCC pat ients who underwent a partial hepatectomy. In IB of the 23 RCC samples , transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tiss ues than in the nontumorous tissues, On the other hand, MMP-2 messenge r RNA(mRNA) was detected in 18 of the 23 cases, Eight of these 18 case s showed more intense expression in the tumorous tissues than in the n ontumorous tissues, whereas the expression levels were lower in the tu morous tissues than in the nontumorous tissues Fn 7 of 18 samples, Wit h respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA i n HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also ten ded to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA exp ression, In addition, the expression of MMP-2 mRNA in nontumorous cirr hotic tissues was significantly higher than in nontumorous tissues fro m patients with chronic hepatitis. Immunohistochemical examinations re vealed that MMP-9 immunoreactivity was the most intense in the HCC cel ls, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration ill HCC.