Elmileik Hashim, Paterson Alan C, Kew Michael C
MRC/University Molecular Hepatology Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
J Surg Oncol. 2005 Sep 15;91(4):258-63. doi: 10.1002/jso.20304.
To ascertain the prevalence of deregulating mutations of beta-catenin gene, and to correlate this with the occurrence of 249(serine) p53 gene mutation and hepatitis B virus infection in southern African Blacks with hepatocellular carcinoma.
Paired cancer/non-cancerous liver tissues from 21 and cancer tissues alone from 20 Black Africans with hepatocellular carcinoma were studied. RT-PCR-SSCP and sequencing were used to detect mutations in exon 3 of the beta-catenin gene, and PCR, restriction endonuclease analysis, and sequencing to detect the p53 gene mutation. Immunostaining was used to identify beta-catenin protein expression in hepatocytes.
No mutations in exon 3 of the beta-catenin gene were found in tumor or non-tumorous tissues. Immunohistochemical staining showed beta-catenin protein expression in membranes and cytoplasm of hepatocytes but not in the nuclei. The 249serine p53 gene mutation was detected in 27.2% of the hepatocellular carcinoma tissues but not in non-cancerous tissues. No correlation was found between beta-catenin mutation and over-expression and 249serine p53 gene mutations or hepatitis B virus surface antigenemia.
Unlike hepatocellular carcinomas in China, Japan, and Europe, deregulating beta-catenin gene mutations do not appear to occur in southern African Blacks with this tumor and do not therefore interact with either the 249serine p53 gene mutation or hepatitis B virus infection in its pathogenesis.
确定β-连环蛋白基因调控突变的发生率,并将其与249(丝氨酸)p53基因突变的发生以及南非黑人肝细胞癌患者的乙型肝炎病毒感染情况相关联。
对21例非洲黑人肝细胞癌患者的癌组织与癌旁肝组织配对样本以及另外20例患者的癌组织样本进行研究。采用逆转录聚合酶链反应-单链构象多态性分析(RT-PCR-SSCP)和测序检测β-连环蛋白基因第3外显子的突变,用聚合酶链反应(PCR)、限制性内切酶分析和测序检测p53基因突变。采用免疫染色鉴定肝细胞中β-连环蛋白的蛋白表达。
在肿瘤组织和非肿瘤组织中均未发现β-连环蛋白基因第3外显子的突变。免疫组化染色显示β-连环蛋白在肝细胞的细胞膜和细胞质中表达,但不在细胞核中表达。249丝氨酸p53基因突变在27.2%的肝细胞癌组织中检测到,而在癌旁组织中未检测到。未发现β-连环蛋白突变及过表达与249丝氨酸p53基因突变或乙肝病毒表面抗原血症之间存在相关性。
与中国、日本和欧洲的肝细胞癌不同,β-连环蛋白基因调控突变似乎未出现在南非黑人的肝细胞癌中,因此在其发病机制中不与249丝氨酸p53基因突变或乙肝病毒感染相互作用。