Retinoblastoma. Immunohistochemistry and cell differentiation

Tumor from eight enucleated eyes was analyzed by immunohistochemistry, using a panel of specific antibodies including interphotoreceptor retinoid-binding protein (IRBP), S-antigen (S-Ag), opsin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), laminin, and vimentin. In addition, immunoelectron microscopy and enzyme-linked immunosorbent assay (ELISA) for IRBP were performed. Immunohistochemical staining disclosed the most pronounced labeling of tumor cells with NSE and IRBP antibodies. A correlation was found between the degree of tumor differentiation and amount of IRBP, a protein specifically synthesized by photoreceptor cells. Moderate labeling of the better differentiated tumors was also observed with antibodies against S-Ag and focal labeling in a few tumors with opsin antibodies. Anti-GFAP labeling was limited to a smaller number of reactive glial cells and perivascular glial cells. These data indicate the essential neuronal nature of retinoblastoma tumor cells in situ as well as at least partial photoreceptor-like features, as shown by the presence of recognized photoreceptor cell markers (IRBP, S-Ag, opsin). Tissue culture studies using the human Y-79 retinoblastoma cell line also demonstrate that the tumor cells are primitive multipotential retinoblasts capable of at least partial differentiation along neuronal, glial, or pigment epithelial cell lines.