Ruck Peter, Xiao Jia-Cheng
Institute of Pathology, University of Tübingen, Tübingen, Germany.
Med Pediatr Oncol. 2002 Nov;39(5):504-7. doi: 10.1002/mpo.10175.
The principles of tumor biology suggest that hepatoblastoma is derived from a pluripotent stem cell. Our studies were undertaken to investigate this tumor for the presence of cells with morphologic and immunophenotypic features of the oval cells of rodents that are thought to be closely related to hepatic stem cells.
Hepatoblastomas of various subtypes were investigated by electron microscopy and immunoelectron microscopy with antibodies against cytokeratin 7, in the liver a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation. Immunohistochemical investigations were performed with the antibodies OV-1 and OV-6, which recognize antigens associated with oval cells.
OV-1 stained scattered cells in seven of 12 tumors investigated and OV-6 in nine. Small epithelial cells (SEC) with the ultrastructural features of the oval cells were found by electron microscopy. They were characterized by small size (7-18 microm), often an oval shape, tonofilament bundles, and tight junctions or desmosome-like junctions. SEC were found in small numbers in areas of fetal differentiation and in moderate numbers in areas of embryonal differentiation. In small cell hepatoblastoma, nearly all the tumor cells exhibited SEC-like features. Immunoelectron microscopy revealed coexpression of cytokeratin 7 and albumin by SEC.
SEC with ultrastructural and immunophenotypic features exhibited by oval cells, i.e., hepatic stem-like cells, are found in hepatoblastoma. Their numbers vary with the differing degrees of differentiation seen in the various subtypes. The findings further support the hypothesis that hepatoblastoma is derived from a pluripotent stem cell.
肿瘤生物学原理表明肝母细胞瘤源自多能干细胞。我们开展研究以调查该肿瘤中是否存在具有啮齿动物卵圆细胞形态和免疫表型特征的细胞，这些卵圆细胞被认为与肝干细胞密切相关。
运用电子显微镜和免疫电子显微镜，使用针对细胞角蛋白7（一种胆管分化标志物）和白蛋白（一种肝细胞分化标志物）的抗体，对各种亚型的肝母细胞瘤进行研究。使用识别与卵圆细胞相关抗原的抗体OV - 1和OV - 6进行免疫组织化学研究。
在所研究的12个肿瘤中，7个肿瘤的OV - 1染色显示散在细胞，9个肿瘤的OV - 6染色显示散在细胞。通过电子显微镜发现了具有卵圆细胞超微结构特征的小上皮细胞（SEC）。它们的特点是体积小（7 - 18微米），通常呈椭圆形，有张力丝束，以及紧密连接或桥粒样连接。SEC在胎儿分化区域数量较少，在胚胎分化区域数量中等。在小细胞型肝母细胞瘤中，几乎所有肿瘤细胞都表现出SEC样特征。免疫电子显微镜显示SEC同时表达细胞角蛋白7和白蛋白。
在肝母细胞瘤中发现了具有卵圆细胞即肝样干细胞所表现出的超微结构和免疫表型特征的SEC。它们的数量因不同亚型中所见的不同分化程度而有所变化。这些发现进一步支持了肝母细胞瘤源自多能干细胞的假说。
