Significance of MLH1 and p53 expression in HBV related- hepatocellular carcinoma
WANG Peixiao1,2,ZHANG Qing2,ZHANG Li3,ZHANG Hui4,CHEN Hong2, HUANG Lihong5
1.Graduate Division of Xinxiang Medical University,Xinxiang 453003,China; 2.Institute of Organ Transplantation, 5.The Graduate Student Affairs Office,General Hospital of Chinese People’s Armed Police Forces, Beijing 100039,China; 3.First Department of Surgery, Shaanxi Provincial Corps Hospital of Chinese People’s Armed Police Forces, Xi’an 710054, China; 4.Department of Gastroenterology ,Luoyang Dongfang Hospital,Luoyang 471003,China
Abstract:Objective To study the expression of MLH1 and p53 in HBV related- hepatocellular carcinoma(HCC), both of the specificity of the expression. Method Objects were 238 patients of HBV related-HCC with cirrhosis in this hospital who had been in the liver transplantation operation from 2003 to 2013. We examined the expression of MLH1 and p53 in 238 patients with HCC and adjacent tissues by immunohistochemistry.As the normal controls were normal liver tissue and benign liver disease. Results The expression of theMLH1postive in the HCC tissues was 31.09%(74/238), with 26.05%(62/238) in cancer adjacent tissues,with 48.00%(12/25)in benign liver diseases tissues. The expression in each group had no significant difference (P=0.053). However,by clinicopathologic rank correlation analysis, the expression of MLH1 was associated with tumour recurrence after liver transplantation (r=-0.159,P=0.014)and the AFP levels (r=0.221, P=0.001),and had certain trend with Edmondson-Steiner Grading(P=0.060)and TNM(P=0.065). The expression of the p53 postive in the HCC tissues was 47.06%(112/238),with 0.84%(2/238)in the cancer adjacent. However, the expression of benign liver diseases tissues were all negative.The expression of p53 protein in tumour tissues was significantly higher than that in cancer adjacent tissues and benign liver diseases tissues (P=0.000),There was association between expression of p53 and vascular invasion (P=0.053) and tumorons numbers (P=0.051). Conclusion Down-regulation of MLH1 expression at the mRNA and protein levels is observed in association with developing hepatocellular carcinoma and relapses. MLH1 has significant correlation with p53.
Matsukura S, Miyazaki K, Yakushiji H. Combined loss of expression of O6-methylguanine-DNA methyltransferase and hMLH1 accelerates progression of hepatocellular carcinoma[J]. J Surg Oncol, 2003,82(3): 194-200.
Matsukura S, Soejima H, Nakagawachi T, et al. CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection[J]. Br J Cancer,2003, 88(4): 521-529.
[5]
Matsukura S, Miyazaki K, Yakushiji H. Combined loss of expression of O6-methylguanine-DNA methyltransferase and hMLH1 accelerates progression of hepatocellular carcinoma[J]. J Surg Oncol, 2003,82(3): 194-200.
[7]
Wani Y, Notohara K, Tsukayama C. Reduced expression of hMLH1 and hMSH2 gene products in high-grade hepatocellular carcinoma[J]. Acta Med Okayama, 2001,55(2): 65-71.
[6]
Matsukura S, Soejima H, Nakagawachi T, et al. CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection[J]. Br J Cancer,2003, 88(4): 521-529.
[8]
Li Z, Zhang H, Yang J. Promoter hypermethylation of DNA damage response genes in hepatocellular carcinoma[J]. Cell Biol Int, 2012, 36(5): 427-432.
[9]
Helal T E, Khamis N S, El-Sharkawy T M. Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt[J]. APMIS, 2010,118(12):934-940.
[7]
Wani Y, Notohara K, Tsukayama C. Reduced expression of hMLH1 and hMSH2 gene products in high-grade hepatocellular carcinoma[J]. Acta Med Okayama, 2001,55(2): 65-71.
Helal T E, Khamis N S, El-Sharkawy T M. Immunohistochemical expression of mismatch repair genes (hMSH2 and hMLH1) in hepatocellular carcinoma in Egypt[J]. APMIS, 2010,118(12):934-940.
Levine A J, Oren M. The first 30 years of p53: growing ever more complex[J]. Nat Rev Cancer,2009, 9(10): 749-758.
[14]
Mohamed W S, Omar M M, Khayri T M. Assessment of the Proliferative Marker Ki-67 and p53 Protein Expression in HBV- and HCV-related Hepatocellular Carcinoma Cases in Egypt[J]. Int J Health Sci (Qassim),2008, 2(1): 27-34.
Greenblatt M S, Feitelson M A, Zhu M, et al. Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas[J]. Cancer Res,1997, 57(3): 426-432.
Mohamed W S, Omar M M, Khayri T M. Assessment of the Proliferative Marker Ki-67 and p53 Protein Expression in HBV- and HCV-related Hepatocellular Carcinoma Cases in Egypt[J]. Int J Health Sci (Qassim),2008, 2(1): 27-34.
[15]
Greenblatt M S, Feitelson M A, Zhu M, et al. Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas[J]. Cancer Res,1997, 57(3): 426-432.