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Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2005; 11(29): 4587-4591
Published online Aug 7, 2005. doi: 10.3748/wjg.v11.i29.4587
Expression and hypermethylation of p27kip1 in hepatocarcinogenesis
Pu-Ping Lei, Zong-Ji Zhang, Li-Juan Shen, Jin-Yun Li, Qiong Zou, Hua-Xian Zhang
Pu-Ping Lei, Zong-Ji Zhang, Li-Juan Shen, Qiong Zou, Hua-Xian Zhang, Department of Pathology, Kunming Medical College, Kunming 650031, Yunnan Province, China
Jin-Yun Li, Department of Pathology, the Second Affiliated Hospital, Kunming Medical College, Kunming 650032, Yunnan Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Science Foundation of Yunnan Province, China, No. 2000C0058M, and Scientific Research Foundation of the Education Department of Yunnan Province, No. 0011010
Correspondence to: Dr. Li-Juan Shen, Department of Pathology, Kunming Medical College, Kunming 650031, Yunnan Province, China. wycslj@public.km.yn.cn
Telephone: +86-871-5338845 Fax: +86-871-5151197
Received: July 28, 2004
Revised: January 7, 2005
Accepted: January 14, 2005
Published online: August 7, 2005
Abstract

AIM: To study the expressions of p27kip1 protein and p27mRNA, the hypermethylation of p27kip1 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 p27kip1 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, χ2 = 7.664). The positive rate of p27kip1 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 p27kip1 mRNA also significantly decreased in HCC compared to that in the other groups (P = 0.000, χ2 = 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.

CONCLUSION: 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.

Keywords: Hepatocellular carcinoma, p27kip1, Immunohist-ochemical staining, In situ hybridization, Hypermethylation