Expression of the human nephron differentiation molecules in renal cell carcinomas. The authors tested frozen sections from 28 renal cell carcinomas (RCC)--21 clear, 1 eosinophilic, 4 basophilic, and 2 spindle-shaped cell type--with monoclonal antibodies (MAb) reacting against cytokeratin, vimentin, CD24, CALLA/CD10, villin, CD26, and HLA class I and class II molecules. These molecules are markers of specific segments of the mature kidney, and their loss or acquisition reflects the different steps of human nephrogenesis. KI67 MAb was used to evaluate cell-proliferating activity. All RCC cases expressed cytokeratin. Coexpression of vimentin was observed in 21 of 28 cases. Whether of clear or chromophilic type, all tumoral cells strongly expressed CD24 molecule, present on primitive blastema cells. All clear-type RCCs expressed CALLA/CD10 and 60% were also villin positive; some were faintly positive for CD26. CALLA, villin, and CD26 were not detected in basophilic cell type. HLA class I molecules were variably expressed in almost all cases, but HLA class II were never detected on tumoral cells. Except for the spindle-shaped population, cell-proliferating activity was low. These results favor the hypothesis that RCCs derive from cells that have 'recovered' the different options of metanephric differentiation. Clear cells show evidence of maturation toward proximal type, while basophilic cells do not. It would be of interest to evaluate the usefulness of serum measurements of villin and/or CALLA as markers in clear cell-type RCC. 