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W. Gao, D. Collins, B. L. Gallie, J. O'Brien JM, G. B. Hubbard, M. Chrenek, S. Kang, H. Grossniklaus; Pathobiologic Changes in Diffuse Anterior Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):16. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the pathobiologic changes in diffuse anterior retinoblastoma, including DNA mutations and cytokine signaling.
The eyes of two patients who underwent enucleation for diffuse anterior retinoblastoma were evaluated. In one patient, DNA was sequenced from the fresh tumor and patient’s blood. Part of the RB1 exon was sequenced from the formalin fixed, paraffin embedded tumor from the second patient. Both eyes were immunostained for VEGF, TGFβ, HIF-1 and iNOS. Immunostaining patterns of intraretinal tumor, vitreous seeds and anterior chamber seeds were graded as 0 to +++ (none, mild, moderate, strong).
RB1 gene molecular analysis in the first patient showed c.763C T(R255)X mutation in both the tumor and peripheral blood and c.1572delA in the tumor compared with a normal allele in the peripheral blood (heterozygous deletion of an "A" nucleotide in exon 17). Partial sequencing of RB1 in the second patient showed a possible isoleucine to valine heterozygous missense mutation in exon 25. Immunofluorescent staining of both tumors showed strong TGFβ expression in tumor seeds and no expression in intraretinal tumor, strong VEGF expression in tumor seeds and mild expression in intraretinal tumor, and no HIF-1 or iNOS expression.
Diffuse anterior retinoblastoma may be result from a germline mutation. Sequential events resulting in VEGF expression of tumor seeds occurs as the tumor spreads from the retina into the aqueous. These events do not appear to result from ischemia and indicate that retinoblastoma seeds into the anterior chamber via a micrometastatic process.
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