乙型肝炎、肝硬变和肝癌中HBxAg的表达及其在肝癌发生中的作用

对３７９例良、恶性肝组织进行的免疫组织化学研究显示，３３％的慢性迁延性肝炎（６／１８）、７６％的慢性活动性肝炎（２６／３４）、９２％的肝硬变（５７／６２）和９７％的肝细胞性肝癌（ＨＣＣ）（５８／６０）中有ＨＢｘＡｇ表达，阳性率高于ＨＢｓＡｇ或ＨＢｃＡｇ。癌周肝中的ＨＢｘＡｇ阳性率显著高于非癌周肝。与其它２种ＨＢＶ抗原不同，ＨＢｘＡｇ表达在细胞类型上有较明显的选择性，在肝小多角细胞（ＳＰＬＣ）、小细胞性不典型增生（ＳＣＤ）及ＨＣＣ中较强。与ＩＧＦⅡ、ｃ－ｅｒｂＢ－２、ｃ－ｍｙｃ和ＥＧＦ－Ｒ表达进行的对照研究表明ＨＢｘＡｇ与ＩＧＦⅡ和ｃ－ｅｒｂＢ－２这２种ＨＣＣ发生相关基因的表达关系密切。ＰＣＮＡ染色结果显示ＨＢｘＡｇ阳性组织的细胞增殖活性显著高于ＨＢｘＡｇ阴性组织。我们的结果还表明ＨＢｘＡｇ表达与肝细胞不典型增生的发生和进展有关、提出ＨＢＶＸ基因可能通过其表达产物（ＨＢｘＡｇ）首先激活ＩＧＦⅡ、ｃ－ｅｒｂＢ－２基因，继而引起显著的ＳＰＬＣ增生和ＳＣＤ而参与ＨＣＣ发生的．

STUDY ON EXPRESSION OF HBxAg AND IN HEPATITIS B, LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA

An immunohistochemical investigation has been made in the benign and malignant liver tissues of 379 cases. X gene product (HBxAg) of Hepatitis B virus (HBV) was observed in 33% of chronic persistent hepatitis (6/18), 76% of chronic active hepatitis (26/34), 92% of liver cirrhosis (57/62) and 97% of hepatocellular carcinoma (HCC) (58/60). The positive rates were shown to be higher significantly than those of HBsAg or HBcAg. It was also found that the positive rate of HBxAg was significantly higher in the pericancerous liver tissue than in the non-perican cerous tissue. The distribution pattern of HBxAg was found tobe different from that of HBsAg or HBxAg expression was observed to have thepower of selecting the cell types, especially in small polygonal liver cells (SPLCs), the bepatocytes in small-cell dysplasia (SCD) and HCC cells. A comparative study of HBxAg expression and IGF II, c-erbB-2, c-myc, EGF receptor expression indicated that the HBxAg expression was related to those of IGF II and and c-erbB-2 oncogene. The immunostaining withproliferating cell nuclear antigen (PCNA) antibody showed that the HBxAg-positive livertissue had a higher cell proliferating activity than the HBxAg-positive liver HBxAs expression was found to be closely related to the development and progression of liver cell dysplasia. We suggested that HBV X gene may play an important role in SPLC proliferation. SCD and HCC genesis by the transactivation of IGF II and c-erbB-2 oncogene.