Haruna Y, Hayashi N, Kamada T, Hytiroglou P, Thung S N, Gerber M A
Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699.
Cancer. 1994 May 1;73(9):2253-8. doi: 10.1002/1097-0142(19940501)73:9<2253::aid-cncr2820730904>3.0.co;2-9.
Epidemiologic studies have suggested a strong association between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). To investigate the possible role of HCV in the pathobiology of HCC, the authors studied the expression of HCV in 10 cases of HCC with chronic HCV infection.
The core, envelope, and nonstructural (NS) 3 and 5 proteins were localized in liver and tumor tissues by the immunoperoxidase technique using mouse monoclonal antibodies to recombinant proteins or synthetic peptide of HCV. In addition, the positive and negative strands of HCV RNA were detected in the tissues by strand-specific reverse transcription/double polymerase chain reaction using primers for the 5'-nontranslated region.
The HCV proteins were expressed in three of nine HCC specimens tested (the core protein in three HCC, the envelope, NS3 and NS5 proteins in one HCC) and in two of nine nontumorous liver specimens adjacent to the HCC (the core protein in two specimens, envelope, NS3 and NS5 proteins in one specimen). Positive-stranded HCV RNA was detected in all tumorous and nontumorous specimens except in one tumor. Negative-stranded HCV RNA was found in six of nine HCC tested and in all nontumorous livers.
These findings suggest that HCV persists in hepatocytes during malignant transformation, although secondary infection of tumor cells by HCV cannot be excluded. Some HCC appear to support replication and expression of HCV.
流行病学研究表明,慢性丙型肝炎病毒(HCV)感染与肝细胞癌(HCC)的发生之间存在密切关联。为了研究HCV在HCC病理生物学中的可能作用,作者对10例慢性HCV感染的HCC病例中HCV的表达进行了研究。
使用针对HCV重组蛋白或合成肽的小鼠单克隆抗体,通过免疫过氧化物酶技术将核心、包膜以及非结构(NS)3和5蛋白定位在肝脏和肿瘤组织中。此外,使用针对5'-非翻译区的引物,通过链特异性逆转录/双重聚合酶链反应在组织中检测HCV RNA的正链和负链。
在检测的9个HCC标本中有3个表达了HCV蛋白(3个HCC中表达核心蛋白,1个HCC中表达包膜、NS3和NS5蛋白),在与HCC相邻的9个非肿瘤肝脏标本中有2个表达了HCV蛋白(2个标本中表达核心蛋白,1个标本中表达包膜、NS3和NS5蛋白)。除1个肿瘤外,在所有肿瘤和非肿瘤标本中均检测到正链HCV RNA。在检测的9个HCC中有6个以及所有非肿瘤肝脏中发现了负链HCV RNA。
这些发现表明,尽管不能排除HCV对肿瘤细胞的继发感染,但HCV在恶性转化过程中持续存在于肝细胞中。一些HCC似乎支持HCV的复制和表达。