Characterization of cytoskeletal components in epithelial and mesenchymal liver tumors by electron and immunofluorescence microscopy.

Abstract

Intermediate-sized filaments and microfilaments were studied by electron and immunofluorescence microscopy using antibodies to their constitutive proteins in various rat liver tumors induced by nitrosamines. Hepatocellular carcinomas contained both tonofilaments and microfilaments which could be demonstrated light-microscopically by antibodies to prekeratin and actin, respectively, and were predominantly localized, in a somewhat irregular pattern, in peripheral cytoplasmic regions. The hepatocellular tumors did not show significant amounts of intermediate-sized filaments of the vimentintype. Cholangiofibromas exhibited, within the epithelial duct component, actin-positive microfilaments organized in a terminal web and prekeratinpositive tonofilaments, the latter often being present in large amounts. By contrast, the mesenchymal component of the cholangiofibromas and the cells of angiosarcomas or undifferentiated sarcomas were characterized by intermediate filaments stainable with antibodies against vimentin, but not with those to prekeratin. In addition to vimentin, the mesenchymal tumors contained small amounts of actin. In many cells of the sarcomas a pronounced accumulation of intermediate-sized filaments of the vimentin type, frequently forming whorl-like aggregates, was evident. The characteristic “vimentin storage cells”, many of which were readily identifiable in H&E sections by large fibrillar cytoplasmic inclusions, were pathognomonic for sarcomas, especially for angiosarcomas. The detection of early stages of angiosarcomas by antibodies to vimentin was also facilitated. Our results do not support the concept that presence of an excess of contractile proteins such as actin is an important prerequisite for the metastasic spread of malignant cells. The observations show that antibodies to the different classes of intermediate filaments are a powerful tool for the classification and differential diagnosis of epithelial and mesenchymal tumors of the liver and probably also of other sites. The accumulation of prekeratin in many ductular cells of the cholangiofibromas and the considerable storage of vimentin in sarcoma cells seem to indicate a severe disturbance of the cell metabolism which might be related to the neoplastic transformation.