Retinoblastoma, the most common intraocular
tumor of childhood, is a
malignant neoplasm that arises during
retinal development. The embryonal cell target for neoplastic transformation is not yet clearly defined. To better understand the histogenetic potential of this
tumor, the expression of photoreceptor and glial cell-associated
proteins were examined in 22 primary
retinoblastomas.
Interphotoreceptor retinol-binding protein (IRBP), cone and
rod opsins were selected as the photoreceptor specific
proteins due to their different temporal patterns of expression during normal
retinal development. Neoplastic Müller cell differentiation, and non-neoplastic reactive astrocytes were identified using cellular
retinaldehyde binding-protein (CRAlBP), and
glial fibrillary acidic protein (GFAP), respectively. Photoreceptor
proteins were present in 16 cases and showed different cellular patterns of expression. IRBP and
cone opsin were usually abundant. Although
rod opsin was clearly identified in eight
tumors, its expression was more restricted than either IRBP or
cone opsin. This differential pattern of expression, opposite to the normal pattern of photoreceptor gene expression in the adult retina, corresponded to a marked decrease in
mRNA for
rod opsin.
Cone opsin and IRBP colocalized in fleurettes demonstrating that neoplastic human cone cells are capable of IRBP synthesis. Müller cell differentiation was present in 12 of the 16 cases in which photoreceptor
proteins were detected. In contrast, GFAP was only present in reactive, stromal astrocytes associated with blood vessels. Our data suggest that the
retinoblastoma has the histogenetic potential of the immature neural
retinal epithelium which can give rise to both photoreceptor and Müller cell lineages. The differential expression of cone and rod phenotypes in
retinoblastoma is consistent with the "default" mechanism of cone cell differentiation.