Expression and hypermethylation of p27 kip1 in hepatocarcinogenesis.
OBJECTIVE
To study the expressions of p27 kip1 protein and p27mRNA, the hypermethylation of p27 kip1 and the relation between them in various stages of hepatocarcinogenesis.


METHODS
p27 protein and p27mRNA were detected by immunohistochemical staining and in situ hybridization respectively in 68 cases of normal liver, liver cirrhosis, pericancerous cirrhosis and hepatocellular carcinoma (HCC). The hypermethylation of p27 kip1 was detected by methylation-specific PCR (MSP) in 44 cases of normal liver, liver cirrhosis, and HCC.


RESULTS
The positive rate of p27 protein was 66.7% (4/6) in normal liver, 60.0% (6/10) in liver cirrhosis, 50.0% (12/24) in pericancerous cirrhosis and 21.4% (6/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27 protein significantly decreased in HCC compared to that in the other groups (P = 0.006, chi2 = 7.664). The positive rate of p27 kip1 mRNA was 83.3% (5/6) in normal liver, 70.0% (7/10) in liver cirrhosis, 75.0% (18/24) in pericancerous cirrhosis and 25.0% (7/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27 kip1 mRNA also significantly decreased in HCC compared to that in the other groups (P = 0.000, chi2 = 16.600). In addition, there was a significant correlation between the expression of p27 protein and p27mRNA in the integrated group of normal liver and liver cirrhosis. However, no significant correlation was found between pericancerous cirrhosis and HCC. Using MSP, we found that 1 HCC in 44 cases (including 6 cases of normal liver, 10 cases of liver cirrhosis and 28 cases of HCC) was methylated, whose p27 protein and p27mRNA were negative.


CONCLUSIONS
The reduction or loss of p27 protein and p27mRNA are potentially involved in hepatocarcinogenesis. The hypermethylation of p27 might lead to the loss of p27mRNA transcription.
Lei
Pu-Ping
PP
Department of Pathology, Kunming Medical College, Kunming 650031, Yunnan Province, China.
Zhang
Zong-Ji
ZJ
Shen
Li-Juan
LJ
Li
Jin-Yun
JY
Zou
Qiong
Q
Zhang
Hua-Xian
HX
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D018899:CpG Islands / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000503:physiopathology
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27