The Expression And Significance Of P63 And MDM2 In Hepatocellular Carcinoma Tissues

Objective:P63 is one of family p53 which is a classic anti-oncogene,but theirs functions aren't same absolutely. The absence or mutation of p63 gene will lead to a series of syndromes of development malformations about the epidermis of embryon's facial surface and the limbs. Except for the contribution in cell differentiation and development,the research prove that p63 gene seldom mutate in the malignant tumor. Moreover, some isomers of p63 protein are considered to be anti-oncogenes in the origin and development of tumor,and the others, oncogenes.Mdm2, murine double minute 2,is an oncogene.The researches manifest that it can makes p53 deactivate and results in cancers by combining with p53 because of the regulation of p53-mdm2 degenerative feedback in humen bodies,and that it could have the carcinogenesis itself.However,there are contrary conclusions about mdm2 or mdmX regulating the level of p63 protein.Can mdm2 combine with p63 and what is the effect of the conjugate if they could, about which all around researches are disputing. In this experiment , through the method of Immunohistochemistry , we investigate the expressions of p63 and mdm2 in order to explore their correlation in tumorigenesis and progression,and also to initially approach the role and clinical significance in hepatocellular carcinomas.Methods:Paraffin embedded tissues from 41 hepatocellular carcinomas (all were proved by pathohistology.All the patients had the operation first time and didn't accept any radiotherapy or chems before operation)and 14 non-neoplastic liver Parenchyma(8 from sclerotic liver tissues and 6 from normal liver tissues)were collected in this research.By means of immunohistochemical SP method,the expressions of p63 and mdm2 were compared between the hepatocellular carcinoma and non-neoplastic 1iver parenchyma tissues.Positive control was the tissue section which expressed positively and negative control was normal liver samples which were definite in this experiment.The blank were the samples which had not first antibody fluid in the incubation process of antigen-antibody. The cellular nucleus of positive cell should be buffy.The class of dyeing referred to the scoring method of"Shimizu".All the results were dealt by SPSS13.0 and analyzed byχ2 test and spearman correlation.Results:1. The number of the positive expression of p63 in hepatocellular carcinoma tissues was 27, and the expression rate was 65.9%;there was no expression in sclerotic liver and normal liver tissues;the difference between the hepatocellular carcinoma tissues and non-neoplastic liver parenchyma tissues was significan(tχ2=18.11,P=0.000).In both well and moderately differentiated group and poorly differentiated group of the hepatocellular carcinoma tissues,the positive expression rates were 50% and 88.24%, respectively, with significant difference(χ2=6.470,P=0.011).In both tumor's diameter≥5㎝ group and tumor's diameter<5㎝ group of the hepatocellular carcinoma tissues, the positive expressions rates were 80.95% and 50%,with significant difference(χ2=4.364,P=0.035).2. The number of the positive expression of mdm2 in hepatocellular carcinoma tissues was 31,and the expression rate was 73.2%; it was expressed in 2 out of the 6 sclerotic liver tissues;no expression was found in the normal liver tissues. The difference between the hepatocellular carcinoma tissues and sclerotic liver tissues was significant(χ2=7.797,P=0.007);no significant difference in the normal liver and sclerotic liver tissues(χ2=1.750,P>0.05).The positive expression of mdm2 was different in different pathological grade(sχ2=6.054,P=0.014),and high level in well and moderately differentiated group(87.50%).Conclusion:1. P63 and mdm2 were expressed at high levels in the majority of hepatocellular carcinoma tissues.2. P63 is an oncogene in hepatocellular carcinoma tissues and correlates with different pathological grades and size of the tumor:it expresses remarkably in the poorly differentiated group and tumor's diameter≥5㎝ group.This indicates that p63 plays an essential role in the origin and development of hepatocellular carcinoma and may be valuable for diagnosisand prognosis.3. The positive expression rate of mdm2 involves with different pathological grades of the tumor:the expression level is high in the well and moderately differentiated group. Therefore,mdm2 has the value for evaluating malignancy and prognosis.4. There is no correlation between the expressions of p63 and mdm2 in hepatocellular carcinoma tissues.