Study of the expression of matrix metalloproteinase and its tissue inhibitor in hepatocellular carcinoma

Objective To study the expression of matrix metalloproteinase (MMP) and the tissue inhibitor of matrix metalloproteinase (TIMP) in hepatocellular carcinoma (HCC) and its relation with the prognosis of patient. Methods MMP 1,MMP 2,MMP 9 and TIMP 2 in human HCC tissue and HCC cell line were measured and quantified with immunohistochemistry, Northern blot hybridization and image analysis. Results MMP 1,MMP 2 and MMP 9 were localized in the cytoplasm of tumor cells. The 5 years survival rate were markedly higher in the cases of MMP 1 negative, MMP 9 negative, both MMP 1 and MMP 2 negative or both MMP 1 and MMP 9 negative staining than that of the positive cases ( P 0.05). In vitro the expression of MMP 9 mRNA in 7721 HCC cells was markedly higher than that in the normal hepatocyte cell line L 02 and 7721 HCC cells reversed with all trans retinoid acid (RA 7721), while the level of the expression of MMP 2 mRNA in 7721 HCC cells was only slightly higher than that of L 02 cells. In contrast to MMP 9, the expression of TIMP 2 mRNA in 7721 cells was significantly lower than that of L 02 cells. Conclusion The expressions of MMP 1 mRNA and MMP 9 mRNA was related to prognosis of patient. The increase of the expression of MMP 9 mRNA and the decrease of TIMP 2 mRNA might be the major basis of the tumor invasion and metastasis with a poor prognosis of HCC.