RETINOBLASTOMA - CELL OF ORIGIN

Objectives: To apply modern techniques of molecular cell biology and t o revisit the old question of the cell of origin for retinoblastoma in hopes of gaining a better understanding of the retinoblastoma gene's antioncogenic mechanisms. Methods: Twenty-two consecutively accessed r etinoblastomas were examined with immunocytochemical techniques for nu merous retinal proteins. Both single and double labeling were used. En zyme histochemistry for carbonic anhydrase was used as well. Results: Differentiated areas of the tumors contained abundant Mullerlike cells . Fleurettes stained mostly for red and green cone-specific antibodies while features of blue cones and rods predominated in areas with high cytoplasmic-to-nuclear ratios but no fleurettes. All of the different iated neoplastic cells were either photoreceptors or Muller's cells. N o other retinal cell types were found. Conclusions: The cells of retin oblastoma are capable only of bipotential differentiation, ie, Muller' s cells and photoreceptors. Given this and recent findings concerning retinal embryogenesis, we argue for the rod photoreceptor as the cell of origin. A possible role for the retinoblastoma gene product is disc ussed.