ROLE OF TRANSFORMING GROWTH FACTOR ALPHA IN HEPATOCARCINOGENESIS

转化生长因子α（TGF-α）以高水平表达 在人肝细胞癌（HCC）中，它可能是一种机制的一部分， B型肝炎病毒（HBV）通过其引起HCC。 研究仍在继续， TGF-α在肝癌发病中的作用分析。 先前 该实验室的工作显示，在正常人中TGF-α表达水平较高， 大多数人HCC中TGF-α基因的上调， 用B型肝炎病毒转染后的肝母细胞瘤细胞系 （HBV）。 肝细胞癌（HCC）通常由两种或更多种不同的肿瘤细胞组成。 在同一肿瘤的不同明确区域的组织学分级， 同一个病人。 这在理论上提供了一个模型， 来自HCC发展的不同阶段的组织。 HCC和邻近 来自25名患者的非肿瘤性肝脏，其中15名患者的肿瘤含有 至少两种不同的组织学分级，进行了评价， 转化生长因子-α（TGF-α）的表达及其 受体，表皮生长因子受体（EGFR），使用抗生物素蛋白- 生物素-过氧化物酶复合物法 手术切除在 1981年至1992年在库尔斯克大学医院工作。 HBsAg检出率为 肝脏3例（12%）。 25例HCC中有24例（96%）检测到TGF-α， 23/24例（96%）可获得邻近非肿瘤性肝脏。 EGFR检测 25例HCC中16例（64%）和24例邻近非肿瘤性肝脏中17例（71%）。 25例HCC中有15例含有两种不同级别的肿瘤结节 (two其中15个含有三种不同等级的结核）， 分化程度较低的组织学分级，出现在或邻近 第一个肿瘤 在这些情况下，在低分化区域的染色 肿瘤的强度通常低于分化程度较高的 面积（80%的TGF-α病例; 91%的EGFR病例）。 TGF-α和EGFR是 在两个正常的肝脏中没有检测到。 这些数据证实， TGF-α和EGFR的表达经常发生在人HCC中。 此外，检测到更大的染色在更高的 肿瘤的分化部分表明， TGF-α和EGFR的表达可能是人类肿瘤早期阶段的事件， 肝癌发生

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.