The Study Of Midkine And CD34 Expressions In The Tissue And Midkine Expression In The Serum Of Patients With Primary Hepatocarcinoma

Objective:To detect the expressions of MK and CD34 in hepatocellular carcinoma tissues, measure the MK expression in the serum of patients with primary hepatocarcinoma, study their relations to the biological characteristics of primary hepatocarcinoma, clarify the role of MK in the invasion and metastasis of hepatocarcinoma. At the same time, provide evidence to disclose the malignant biological behavior of hepatocarcinoma, and get an objective evaluation and judgment of diagnosis,curative effect and prognosis for patients with hepatocarcinoma.Methods:Specimens were taken from 45 patients with hepatocellular carcinoma, 14 patients with liver cirrhosis and 17 normal liver tissues. The tissues were analysed with the methods of immunohistochemistry, in order to analyse the correlation between their expressions and clinical pathologic features of patients with primary hepatocarcinoma. ELSIA technique was used to measure serum concentration of MK in 46 patients with primary hepatocarcinoma without any treatment before operation and 32 control cases;so as to analyse the correlation between the serum MK level of primary hepatocarcinoma patients with the clinical pathologic characteristics and prognosis. The serum AFP level was also tested at the same time. Result one(immunohistochemistry)1.MK positive expression was 82.2% in hepatocellular carcinoma tissues ,21.4% in liver cirrhosis tissues and 5.9% in normal liver tissues. The MK expression in hepatocellular carcinoma tissues was significantly higher than that in liver cirrhosis and in control group(P <0.001;P<0.001).2. The average value of MVD in the patients with hepatocellular carcinoma , liver cirrhosis and control group was 52.18±9.37;42.21±8.38 and 46.47±8.12 repectively. The MVD expression in hepatocellular carcinoma was significantly higher than that in liver cirrhosis and control group(P<0.01;P<0.05).3. There is no significant difference between the expressions of MK and MVD in liver cirrhosis and that in control group (P>0. 05; P>0. 05) .4. The MK expressions in hepatocellular carcinoma were not related to gender, age, tumor size, membrane integrity, AFP value, differentiation and HBV infection(P>0.05). Meanwhile there were significantly statistic difference between TNM stage , portal vein invasion, satellite focus and lymph node metastasis and MK expressions (P<0.05). The MVD expressions in hepatocellular carcinoma were not related to gender, age, tumor size, AFP value, differentiation and HBV infection(P>0.05), while significantly related with membrane integrity ,portal vein invasion and lymph node metastasis(P<0.05). There were also statistic significance between the MVD expression and the TNM stage and satellite focus.5. The MK expression was positively correlated with the MVD expression in hepatocellular carcinoma tissues(r=0.393, P=0.008<0.01).Result two(ELISA)1.The average serum level of MK was 4.17±2.08ng/ml in the patients with primary hepatocarcinoma, 1.64±2.38ng/ml in control group. The serum concentration of MK in the patients with Primary hepatocarcinoma was significantly higher than that in control group(P<0. 01).2. The serum level of MK was not related to age, gender, tumor size and pathologic type in the patients with primary hepatocarcinoma, but significantly related to TNM stage, differentiation, membrane integrity, AFP value, pathologic grade and lymph node metastasis (P<0. 05).3. The serum level of MK was correlated with the survival rate in the patients with primary hepatocarcinoma(X~2=5.515, P<0.05).4.With the COX regression model we did, the serum MK level may be considered as an indespendent prognosis factor in the patients with primary hepatocarcinoma.Conclusions:1.The expressions of MK and MVD in tumor tissues and in peripheral serum were significantly higher than that in liver cirrhosis and in control group, which may indicate the higher expressions of MK and MVD were linked with the occurrence of primary hepatocellular carcinoma.2. The expression of MK in the hepatocarcinoma tissues was significantly higher than that in liver cirrhosis. MK may take part in the progress from liver cirrhosis to hepatocarcinoma.3. The expressions of MK and MVD were correlated with TNM stage, tumor integrity, portal vein invasion, satellite focus and lymph node metastasis, which may indicate their expressions had the relation with invasion and metastasis of hepatocarcinoma.4. The survival rate in the patients with primary hepatocarcinoma with MK negative expression(≤3.17ng/ml) was significantly higher than that in positive ones(≥3.17ng/ml), which may show that there were close relationship between the expression of MK and prognosis of patients with hepatocarcinoma.5. With the COX regression model, the serum MK level may be considered as an indespendent prognosis factor in the patients with hepatocarcinoma. 6. The combinative analysis of MK and AFP may be more useful to earlier diagnosis, tumor progress and judging prognosis of patients with hepatocarcinoma.