Distribution of vimentin, cytokeratins, and desmosomal-plaque proteins in human nephroblastoma as revealed by specific antibodies: co-existence of cell groups of different degrees of epithelial differentiation

The distribution of cytokeratins, desmosomal-plaque proteins (desmoplakins), and vimentin in nephroblastoma tissue was studied by immunofluorescence microscopy using specific antibodies. In undifferentiated blastema cells, desmosomes, as revealed by antibodies to desmoplakins, preceded the advent of significant amounts of cytokeratins, indicating that desmosomes are early and sensitive markers of epithelial differentiation. Cytokeratin-positive tumor cells were seen in the following distribution patterns: groups of loosely arranged and scattered cells containing only scant cytokeratin fibrils surrounded by negative stroma cells; focal accumulation of cytokeratin-positive cells with cytokeratin-specific cytoplasmic fibril meshwork staining; rosettes of cytokeratin-positive cells without formation of distinct lumina, showing concentration of cytokeratin staining in the center; tubules with distinct lumina made up of cytokeratin-positive cells, with cytokeratin staining concentrated in the subapical cell portions. In cytokeratin-positive cells, the numbers of desmoplakin-positive dots were generally increased; in well-formed tubules, enrichment of desmoplakin-positive spots, corresponding to the subapical skeletal disks, was most conspicuous. Vimentin was demonstrated in stromal areas, but also in blastema cells showing coexpression of desmosomes and vimentin filaments. Moreover, in certain blastema cells, an overlap of cytokeratin and vimentin immunostaining was observed. Epithelial cells of nephroblastoma tubules did not react with vimentin antibodies. Our results show that the appearance of desmosomal plaques, as demonstrated by antibodies to desmoplakins, may be a very early feature of epithelial differentiation, and they also emphasize the value of antibodies to desmoplakins in tumor cell typing and diagnosis.