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Abstract
PURPOSE: To search for differentiation in retinoblastoma toward horizontal cells and retinal neurons other than photoreceptor cells with antibodies to parvalbumin, a horizontal, ganglion, and amacrine cell-associated antigen. METHODS: Fifty formalin-fixed and paraffin-embedded human eyes with an intraocular retinoblastoma and two orbital recurrences were studied using the avidin-biotinylated peroxidase complex method and monoclonal antibody (mAb) PA-235 to parvalbumin. RESULTS: In the retinas of retinoblastoma eyes obtained after birth, horizontal cells at the outer border of the inner nuclear layer and their processes in the inner part of the outer plexiform layer always reacted with mAb PA-235. Immunolabeled ganglion and amacrine cells were found, respectively, in 31 (76%; 95% confidence interval [CI] 60-88) and 15 (37%; 95% (CI 22-53) of the 41 eyes with preserved retinas, whereas bipolar and photoreceptor cells were unlabeled. Undifferentiated and differentiated retinoblastoma cells in all studied specimens were negative for parvalbumin. However, immunopositive horizontal and ganglion cells engulfed by the tumor were present within 36 of the 50 retinoblastomas (72%; 95% CI 58 - 84), which often allowed the tracing of otherwise invisible remnants of former infiltrated retinas. CONCLUSIONS: Parvalbumin is a useful marker for horizontal and ganglion cells in normal and pathologic human retinas, including those entrapped within retinoblastoma. The absence of parvalbumin from tumor cells argues against differentiation similar to that seen in these parvalbumin-positive neurons and subpopulations of amacrine cells from the second trimester onward.