Expression And Clinical Significance Of TIMP-2, MMP-2,CD147 In Hepatocellular Carcinoma

Objective:To explore the expression and clinical prognostic significance of TIMP-2, MMP-2, CD 147 in hepatocellular carcinoma (HCC).Methods:Immunohistochemistry method was applied to detect the expression of TIMP-2, MMP-2, CD147 and CD34 in 118 cases HCC. The value of TIMP-2, MMP-2, and CD 147 in predicting the prognosis of HCC was evaluated by survival analysis. Analysis the expression of TIMP-2, MMP-2 and CD 147 in the role of tumorangiogenesis.Results:1. TIMP-2 was positive in most of specimens with different intensity of staining. There were 51 positive out of 118 patients expressing TIMP-2 in HCC group, and 15 positive out of 100 patients in control group. The difference of two groups had statistieally significance. No significant difference was found in each group when compared by sex, age, HBsAg, AFP, differentiation, tumor diameter, preoperative Child-Pugh classification, TNM classfication. However, significant difference was found in capsule formation, tumor vascular invasion, lymph node metastases.2. There were 84 positive out of 118 patients expressing MMP-2 in HCC group, and 20 positive out of 100 patients in control group. The difference of two groups had statistieally significance. No significant difference was found in each group when compared by sex, age, HBsAg, AFP, differentiation, tumor diameter, preoperative Child-Pugh classification. However, significant difference was found in capsule formation, TNM classfication, tumor vascular invasion, lymph node metastases.3. There were 74 positive out of 118 patients expressing CD 147 in HCC group, and 20 positive out of 100 patients in control group. The difference of two groups had statistieally significance. No significant difference was found in each group when compared by sex, age, HBsAg, AFP, capsule formation, preoperative Child-Pugh classification, TNM classification, lymph node metastases. However, significant difference was found in differentiation, tumor diameter and tumor vascular invasion.4. Kaplan-Meier analysis demonstrated preoperative Child-Pugh classification, tumor differentiation, vascular invasion, TNM classfication, lymph node metastases, TIMP-2 and MMP-2 expression were significant factors influencing the disease-free survival of HCC patients. COX regression showed that preoperative Child-Pugh classification, lymph node metastases, vascular invasion and MMP-2 expression were significant risk factors influencing the disease-free survival of HCC patients.5. CD34 was detected in all specimens. MVD were 68.88±11.65,61.82±9.49, 43.25±5.61 and 36.75±9.75 in TIMP-2(-),TIMP-2(+),TIMP-2(++),TIMP-2(+++) and were 31.35±9.25,38.36±5.43,56.28±11.09,69.33±8.97 in MMP-2(-), MMP-2(+), MMP-2(++), MMP-2(+++) and were 37.64±7.69,40.12±8.65,67.71±9.38, 68.34±3.21 in CD147(-), CD147(+), CD147(++), CD147(+++)respectively. ANOVA analysis showed significant difference among the MMP-2 groups and TIMP-2 groups (p<0.05). The expression of MMP-2 had positive correlation with the expression of MVD and CD147 in HCC. The expression of TIMP-2 had negative correlation with the expression of MVD in HCC.Conclusions:TIMP-2, MMP-2, CD 147 were expressed in HCC at different levels. The expression of MMP-2 was closely associated with tumor vascular invasion.Over-expression of TIMP-2, MMP-2 and CD 147 were an independent risk factor in predicting the metastasis and recurrence of HCC.