Stem-like cells in hepatoblastoma

Abstract

Background: 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.

Procedure: 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.

Results: 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.

Conclusions: 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.