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Cell of Origin

T. Michael Nork, MD; Terry L. Schwartz, MD; Himanshu M. Doshi, MD; Lyndell L. Millecchia, PhD

Arch Ophthalmol. 1995;113(6):791-802.

Abstract
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 Müllerlike 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 Müller's cells. No other retinal cell types were found.

Conclusions
The cells of retinoblastoma are capable only of bipotential differentiation, ie, Müller'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.

Author Affiliations
From the Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison (Dr Nork); and the Departments of Ophthalmology (Drs Schwartz and Millecchia) and Pathology (Dr Doshi), West Virginia University School of Medicine, Morgantown.

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