The Expression Of EMMPRIN, MT1-MMP, CD44v6 And VEGF In Hapatocellular Carcinoma And Their Significance

ObjectiveHepatocellular carcinoma(HCC) is one of the most common cancer in the world. It is a major cause of death from malignant diseases, due to its high incidence malignant behavior and lack of major advancements in treatment. Hepatocellular carcinoma(HCC) has a poor prognosis due to its tendency towards local invasion and subsequent metastasis. A complex series of steps must take place to allow for a single cell to metastasize, which is mediated by multiple proteolytic enzymes, angiogenesis and cellular adhesion. Identifying factors responsible for these steps is essential to invasion and metastasis. We detected expression of extracellular matrix metalloproteinase inducer (EMMPRIN), Membrane-type 1 matrix Metalloproteinase (MT1-MMP), vascular endothelial growth factor (VEGF) and CD44 variance 6(CD44v6) by immunohistochemical method in hepatocellular carcinoma(HCC) tissues. We used them to investigate mechanisms of metastasis to human hepatocellular carcinoma(HCC) tissues. The aim of this study was to examine the expression levels of EMMPRIN ,MT1-MMP, VEGF and CD44v6 in hepatocellular carcinoma(HCC) tissues, and to evaluate the relationship between the expression levels of EMMPRIN , MT1 -MMP, VEGF , CD44v6 and some clinicopathological parameters ,such as tumor size , metastasis, pathological type. We also analysed interrelations of EMMPRIN, MT1-MMP, VEGF and CD44v6 in invasion and metastasis of hepatocellular carcinoma(HCC) and study their malignant behavior and clinical significance.MethodsImmunohistochemical method was used to detect the expressions of EMMPRIN,MT1-MMP, VEGF and CD44v6 in 40 cases of hepatocellular carcinoma and 10 cases of normal liver tissues. Their relationships between the four biological marker and some clinicopathological parameters were analyzed.Results1)The positive rates of EMMPRIN , MT1-MMP, VEGF and CD44v6 in HCC were much higher than those in the normal liver tissues, P<0.01. 2) The positive rates and scorings of EMMPRIN were significantly lower in the cases of well-ormiddle-differentiation,without-metastasis,and maximal dimeter of mass < 5cm than that of poorly-differentiation, with-metastasis,and maximal dimeter of mass≥5cm in the HCC tissues, 3) The expression of CD44v6 in the HCC tissue was significantly correlated with the differentiation of tumor, the portal vein tumor embolus and the presence of extrahepatic metastasis, but not correlated with the diameter of the number , 4) The expression of MT1-MMP and VEGF in the HCC tissue was significantly correlated with the diameter of the number and the metastasis , but not correlated with the differentiation of tumor. 5) There was a positive significant correlation between the expression of EMMPRIN and MT1-MMP, MT1-MMP and CD44V6,CD44V6 and VEGF, MT1-MMP and VEGF protein in HCC.The Spearman coefficient was 0.608, 0.701, 0.506, 0.566. Conclusions: 1) The positive rates of EMMPRIN , MT1-MMP, VEGF and CD44v6 in HCC were much higher than those in the normal liver tissues; 2)The expression of EMMPRIN,MT1-MMP,CD44V6 and VEGF are related to the invasion and metastasis of HCC. These results indicate that they might play an important role in the pathogenesis of HCC. whereas, EMMPRIN,MT1-MMP,CD44V6 and VEGF could be considered as the marker for predicting the metastasis and recurrence of HCC; 3) There was a positive significant correlation between the expression of EMMPRIN and MT1-MMP, MT1-MMP and CD44V6,CD44V6 and VEGF, MT1-MMP and VEGF protein in HCC. They stimulated the malignant behavior of HCC. Detecting the combined expression of them may give an objective indication on judging the biological behavior of the HCC.