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Expression And Hypermethylation Of P27~(kip1) In Human Hepatocarcinogenesis

Posted on:2005-08-05Degree:MasterType:Thesis
Country:ChinaCandidate:P P LeiFull Text:PDF
GTID:2144360125455043Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Objective: To study the expressions of P27klpl protein and p27 mRNA, the hypermethylation of p27klpl and the relation of them, and to explore the molecular mechanism of hepatocarcinogenesis.Methods: P27 protein and p27 mRNA were detected by immunohistochemical staining and hisitu hybridization (ISH) respectively in 68 cases of normal liver, liver cirrhosis, pericancerous cirrhosis and hepatocellular carcinoma (HCC). The hypermethylation of p27klpl were detected by methylation-specific PCR (MSP) in 44 cases.Results: The positive rates of P27 protein were 66.7%(4/6) in normal liver, 60.0%(6/10) inliver cirrhosis, 50.0%(12/24) in pericancerous cirrhosis and 21.4%(6/28) hi HCC. There were nostatistical significance among normal liver, liver cirrhosis and pericancerous cirrhosis (p<0.05),but it was significantly decreased in HCC than the other groups (p<0.05). The positive rates ofp27kipl mRNA were 83.3%(5/6) in normal liver, 70.0%(7/10) in liver cirrhosis, 75.0%(18/24) inpericancerous cirrhosis and 25.0%(7/28) in HCC. As the same as P27 protein, there were nostatistical significance among normal liver, liver cirrhosis and pericancerous cirrhosis (p<0.05),but it was also signigicantly decreased in HCC than the other groups (p<0.05). In addition, thepositive signals of P27 protein were mainly located in cytoplasm in normal liver and livercirrhosis, while it was major located in nuclear in pericancerous cirrhosis and HCC. There wassignificant correlation between the expression of P27 protein and p27 mRNA in the integratedgroup of normal liver and liver cirrhosis, however, no significant correlations in both pericancerous cirrhosis and HCC. By using methylation-specific PCR (MSP), 1 HCC of 44 cases showed hypermethylation, both P27 protein and p27 mRNA were negative in this one HCC case.Conclusions: The reduction or loss of P27 protein and p27 mRNA potentially involved inhepatocarcinogenesis. The hypermethylation of p27 might lead to the loss of p27 mRNA transcription.
Keywords/Search Tags:Liver neoplasm/HCC, p27/p27kipl, Immunohistochemical staining, In situ hybridization, Methylation-specific PCR/MSP
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