ROLE OF TRANSFORMING GROWTH FACTOR ALPHA IN HEPATOCARCINOGENESIS

转化生长因子-α高水平表达 在人类肝细胞癌中；它可能是一种机制的一部分 乙肝病毒(乙肝病毒)通过它引起肝细胞癌。研究仍在继续 转化生长因子-α在肝细胞癌病因中的作用分析上一首 该实验室的研究表明，转化生长因子-α在 大多数人肝癌，以及转化生长因子-α基因在一种 乙肝病毒转染人肝母细胞瘤细胞系的建立 (乙肝病毒)。 肝细胞癌通常由两种或两种以上不同的肿瘤组成。 同一肿瘤不同区域的组织学分级 同一个病人。从理论上讲，这为研究提供了一个模型 来自肝细胞癌不同发展阶段的组织。HCCS和邻接 来自25名患者的非肿瘤性肝脏，其中15名患者的肿瘤包含 至少评估了两个不同的组织学级别 转化生长因子-α的表达及其意义 受体，表皮生长因子受体(EGFR)，使用亲和素- 生物素-过氧化物酶-络合物法。手术切除是在 库鲁姆大学医院1981-1992年间。乙肝病毒表面抗原在 肝脏3/25(12%)。在25例肝细胞癌中有24例(96%)检测到转化生长因子-α 23/24(96%)可获得邻近非肿瘤性肝脏。检测到EGFR 在25例肝细胞癌中，16例(%)和24例癌旁肝组织中有17例(71%)。 25个肝癌中有15个含有两种不同级别的肿瘤结节 (15个结节中有两个含有三个不同级别的结节) 分化较低的组织学分级，发生在肿瘤内部或邻近 第一个肿瘤。在这些情况下，在分化较低的区域进行染色 肿瘤的信号通常低于分化程度较高的肿瘤 面积(80%的病例表达转化生长因子-α；91%的病例表达EGFR)。转化生长因子-α和表皮生长因子受体 在两个正常肝脏中检测不到。这些数据证实了增加的 转化生长因子-α和表皮生长因子受体在人肝细胞癌中的表达较为常见。 此外，检测到的染色越多，越高 肿瘤的分化部分表明表达增加 转化生长因子-α和表皮生长因子受体的表达可能是人类早期阶段的事件 肝癌的发生。

Transforming growth factor alpha (TGF-alpha) is expressed at high levels in human hepatocellular carcinoma (HCC); it may be part of a mechanism by which hepatitis B virus (HBV) causes HCC. Research has continued in the analysis of the role of TGF-alpha in the etiology of HCC. Previous work in this laboratory had shown high levels of TGF-alpha expression in most human HCCs, and an up-regulation of the TGF-alpha gene in a hepatoblastoma cell line after transfection with the hepatitis B virus (HBV). Hepatocellular carcinomas (HCCs) often consist of two or more different histologic grades in separate well-defined areas of the same tumor from the same patient. This theoretically provides a model in which to study tissues from the different stages of HCC development. HCCs and adjacent nontumorous livers from 25 patients, including 15 whose tumors contained at least two different histologic grades, were evaluated for the expression of transforming growth factor-alpha (TGF-alpha) and its receptor, epidermal growth factor receptor (EGFR), using an avidin- biotin-peroxidase-complex method. Surgical resections were performed at Kurume University Hospital between 1981-1992. HBsAg was detected in liver in 3/25 (12%). TGF-alpha was detected in 24 of 25 (96%) HCCs and 23 of 24 (96%) available adjacent nontumorous livers. EGFR was detected in 16 of 25 (64%) HCCs and 17 of 24 (71%) adjacent nontumorous livers. Fifteen of the 25 HCCs contained tumor nodules of two different grades (two of the 15 contained nodules of three different grades) which had a less-differentiated histologic grade, arising within or adjacent to the first tumor. In those cases, staining in the less-differentiated area of tumor was usually less intense than in the more highly differentiated area (80% of cases for TGF-alpha; 91% for EGFR). TGF-alpha and EGFR were not detected in two normal livers. These data confirm that increased expression of TGF-alpha and EGFR occur frequently in human HCC. Furthermore, the detection of greater staining in more highly differentiated portions of the tumors suggests that increased expression of TGF-alpha and EGFR may be events of the early stages of human hepatocarcinogenesis.