Retinoblastoma. Cell of origin

T. M. Nork, T. L. Schwartz, H. M. Doshi and L. L. Millecchia
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, USA.

OBJECTIVES: To apply modern techniques of molecular cell biology and to 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 retinoblastomas were examined with immunocytochemical techniques for numerous retinal proteins. Both single and double labeling were used. Enzyme 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 differentiated neoplastic cells were either photoreceptors or Muller's cells. No other retinal cell types were found. CONCLUSIONS: The cells of retinoblastoma 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 discussed.

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