[Role of functional inactivation of p53 from MDM2 overexpression in hepatocarcinogenesis].
OBJECTIVE
This paper was to evaluate the role of p53 mutation, and p53 and MDM2 proteins expression in hepatocarcinogenesis.


METHODS
Using streptavidin-peroxidase conjugation method (SP), the expression of p53 and MDM2 proteins was observed in 61 cases of primary hepatocarcinomas (HCC) and 59 cases of corresponding paracancerous tissue, among which p53 mutations in exons 5-8 were detected in 21 cases by polymerase chain reaction single-strand confirmation polymorphism analysis (PCR-SSCP).


RESULTS
Positive nuclear p53 and MDM2 immunostainings were demonstrated in 57.38% (35/61) and 26.23% (16/61) of HCC, and 1.69% (1/59) and 3.39% (2/59) of corresponding paracancerous tissue, respectively. The expressions of p53 and MDM2 proteins in HCCs were significantly higher than those in paracancerous tissues (P < 0.01). The expressions of p53 and MDM2 were not significantly correlated (P > 0.05). There were 42.86% (9/21) mutations in exon 7 of p53 gene and no mutation was observed in exons 5, 6, 8 in HCCs and in paracancerous tissues. In cases of p53 mutations, there were 66.67% (6/9) of p53 overexpression and 11.11% (1/9) of overexpression of both p53 and MDM2. MDM2 overexpression also appeared in 25% (3/12) of cases without mutation.


CONCLUSIONS
Mutation of p53 gene and functional inactivation of p53 resulting from MDM2 overexpression play an important role in carcinogenesis of HCC. It is possible that p53 mutations and MDM2 overexpression induced by other mechanisms are involved in carcinogenesis of HCC.
Luo
Y L
YL
Department of Pathology, Xiangya Medical College, Central South University, Changsha 410078.
Cheng
R X
RX
Feng
D Y
DY
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D005091:Exons; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2