Study On The Relationship Of ANXA10,MMP-9,VEGF Expressed In Hepatocellular Carcinoma And Their Relationship With Clinicopathological Features

Objective:Through studying on the difference and relationship of annexin-10( ANXA10), matrix metalloproteinase-9 (MMP-9) , vascular endothelial growth factor (VEGF) expressed in HCCs and their relationship with HCCs clinicopathological features(gender, age, tumor location, tumor diameter, differentiation, liver cirrhosis, clinical T stage); initially reveal the potential function of ANXA10 in HCC's occurrence and development ,and whether the function of ANXA10 are related with cytokines of MMP-9,VEGF which were well known to promote invasion and metastasis of HCC.Methods:Collect 80 cases paraffin specimens which have been diagnosed pathologically hepatocellular carcinoma after surgical resection from April 2008 to August 2009 of our Hospital, the tumor size,diameter, liver cirrhosis determined by the pathology. Every case has adjacent normal liver tissue at least 1cm away from the tumor. Nobody had chemotherapy, radiotherapy or interventional therapy before surgery. 4 slices had been sliced from each paraffin specimen, slice thickness 4μm. The expression of ANXA10,VEGF,MMP-9 had been detected by Two-step immunohistochemical method。According to test results, comparativily analyze the relationship of the different expression of ANXA10,MMP-9 and VEGF with clinicopathologic factors (gender, age, tumor location, tumor size, differentiation, liver cirrhosis, clinical T stage). Using SPSS 13. 0 statistical software for data analysis and chi-square test or correlation analysis were carried out between groups of different indicators,p <0. 05 was statistically significant, testing standard takes two tail.Results:1. The morphological characteristics of ANXA10,MMP-9,VEGF staining(1) The HCC cells which yellow, brown granules could be seen in cytoplasm called ANXA10-positive,cell membrance can be seen stained partly.(2) The HCC cells which yellow, brown granules could be seen in cytoplasm called MMP-9-positive, intercellular substance or cell membrance can be seen stained partly.(3) The HCC cells which yellow, brown granules could be seen in cytoplasm called VEGF-positive, intercellular substance or vascular endothelial cell can be seen stained partly.2. The expression of ANXA10 in HCC and adjacent normal liver tissue, the relation with clinical biological behavior.There are 52 ANXA10- positive in HCCs and 73 in adjacent liver tissues, the positive rates were 65% (52/80),91.3% (73/80) respectively, the former was significantly lower than the latter. The expression in adjacent liver tissues tended to be stronger (81.3%), or similar (15%) ,or weaker(3.8%) than that in HCCs .The expression of ANXA10 in HCC was not related with patient's gender,age,tumor size,tumor location,liver cirrhosis, clinical T stage (p > 0.05), but the degree of differentiation (p <0.05)。3. The expression of VEGF in HCC and adjacent normal liver tissue, the relation with clinical biological behavior.There are 51 VEGF- positive in HCCs and 26 in adjacent liver tissues, the positive rates were 63.7% (51/80),32.5% (26/80) respectively, the former was significantly higher than the latter. The expression in adjacent liver tissues tended to be stronger (12.5%), or similar (60%),or weaker(27.5) than that in HCCs .The expression of VEGF in HCC was not related with patient's tumor size,tumor location,clinical T stage (p > 0.05), but the gender,age,liver cirrhosis and degree of differentiation (p <0.05).4. The expression of MMP-9 in HCC and adjacent normal liver tissue, the relation with clinical biological behavior.There are 64 MMP-9- positive in HCCs and 72 in adjacent liver tissues, the positive rates were 80% (64/80),90% (72/80) respectively, the former was lower than the latter. The expression in adjacent liver tissues tended to be stronger (44%), or similar (18.8%),or weaker(26.3%) than that in HCCs .The expression of MMP-9 in HCC was not related with patient's liver cirrhosis, \degree of differentiation, tumor location(p > 0.05), but the gender,age,tumor size and clinical T stage (p <0.05).5. The correlation between the different expression of ANXA10, MMP-9, VEGF.The correlation of different expression in HCCs: the Pearson correlation coefficient C = 0.322 between ANXA10 and MMP-9,there was significant correlation (p = 0.011); the Pearson correlation coefficient C = 0.296 between ANXA10 and VEGF, no significant correlation(p = 0.094); the Pearson correlation coefficient C = 0.401 between VEGF and MMP-9,there was significant correlation (p = 0.021). The correlation of different expression in adjacent liver tissue: the Pearson correlation coefficient C = 0.321 between ANXA10 and MMP-9,there was significant correlation (p = 0.011); the Pearson correlation coefficient C = 0.202 between ANXA10 and VEGF, no significant correlation(p = 0.368); the Pearson correlation coefficient C = 0.468 between VEGF and MMP-9,there was significant correlation (p = 0.028).Conclusions:1. Compared with adjacent liver tissues, the positive rate and expression intensity of ANXA10 in HCCs were significantly reduced, suggesting that ANXA10's expression deletion or inactivation may be an important feature of malignant transformation of hepatocyte;2. The degree of inactivation of ANXA10 may be One of the factors determined the degree of malignancy of hepatocellular carcinoma;3. ANXA10 may be obstructive to the development of HCC;4. The expression of VEGF,MMP-9 in the HCC significantly higher than non-HCC, this may be reasons for high malignancy ,strong aggressiveness and short survival time of HCC.