Immunocytochemical analysis of Ewing's tumors. Patterns of expression of intermediate filaments and desmosomal proteins indicate cell type heterogeneity and pluripotential differentiation

Abstract

Examples of classical Ewing's tumors ("Ewing's sarcomas") of both skeletal and extraskeletal locations were analyzed for the expression of intermediate filament (IF) and cell junction proteins, with the use of immunofluorescence and immunoelectron microscopy as well as gel electrophoresis. In all 11 tumors examined vimentin filaments were abundant. A type of plaque-bearing small cell junction, which is common in these tumors but difficult to classify by morphologic criteria, was identified by antibodies to desmoplakins as true desmosomes. These were found in all cases, although in a very variable proportion of cells. Some of these junctions were associated with vimentin IFs. In addition, 9 of the cases examined showed scattered or clustered cells expressing the simple-epithelium type cytokeratins 8 and 18. Moreover, 3 cases displayed dispersed or clustered cells producing neurofilaments. The value of these observations, notably the cell type heterogeneity, for the diagnosis of tumors of this group is discussed. The results further indicate that Ewing's tumors are derived from a primitive, pluripotential cell that may differentiate, in variable proportions, into cells with mesenchymal, epithelial, and, more rarely, even neural features, suggesting that this tumor should be regarded as a blastoma, rather than as a true sarcoma.