The Studys Of Genetic Instability, MRNA And Protein Expression Of P57^kip2 In Human Hepatocellular Carcinoma

Objective:To study the loss of hererozygosity(LOH)and microsatellite instability(MSI)of P57^kip2and expressions of P57^kip2mRNA & protein in human hepatocellular carcinoma(HCC)in order to explore the molecular mechanism of hepatocarcinogenesis.Methods:MSI and LOH of three microsatellite locis (D11S1760,D11S922and D11S1338)were detected where the P57^kip2gene is in by using PCR-Polyacrylamide gel electrophoresis-silver staining method in 30 cases of HCC.Immunohistochemistry staining and in situ hybridization(ISH)were also used to show the expression of P57^kip2 protein and mRNA in pericancerous cirrhosis and HCC.Results:1.LOH and MSI detected:LOH was not identified in 30 cases on three microsatellite locies;there were 2 microsatellite locies showing MSI,the total rate of MSI was 16.7%2.Expression of P57^kip2mRNA:There were no expressions in normal liver tissue.Expressions both in pericancerous cirrhosis and hepatocellular carcinoma was 26.67%(8/30).There was significant difference between the expressions in high differentiated HCC tissues,moderately differentiated HCC tissues and low differentiated HCC tissues.3.Expression of P57^kip2protein:There were no expressions in normal liver tissue.Expressions in precancerous cirrhosis and hepatocellular carcinoma was 56.67%(17/30)respectively.There was no significant difference between the expressions in high differentiated HCC tissues, moderately differentiated HCC tissues and low differentiated HCC tissues.4.There was correlation between the MSI of D11S1760 locies and the expression of P57^kip2mRNA;there was correlation between the MSI of D11S1760 locies and the expression of P57^kip2protein.5.There was positive correlation between expression of P57^kip2mRNA and expression of P57^kip2protein.Conclusion:1.The disorder expressions of P57^kip2mRNA and protein indicated that P57^kip2may be involved in hepatocarcinogenesis and prognosis.2.LOH was not identified on three microsatellite locies,which indicated that there may be another reason for the disorder expression of P57^kiP2.3.Two microsatellite locis showed MSI where the P57^kip2gene is in, with the disorder expression of P57^kip2mRNA and protein,indicated that MSI may be one of the reasons that lead to the disorder expression of P57^kip2mRNA and protein in hepatocarcinogenesis and prognosis.4.There was correlation between the MSI of D11S1760 locies and the expression of P57^kip2mRNA and protein,which indicated that MSI of D11S1760 may the specifical marker for the disorder expression of P57^kip2in HCC.