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Histopathological Features and P-glycoprotein Expression in Retinoblastoma

¹From the Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil; and the ²Henry C. Witelson Ocular Pathology Laboratory, Department of Ophthalmology, McGill University, Montreal, Quebec, Canada.

PURPOSE. To investigate the expression of P-glycoprotein (P-gp) in retinoblastoma specimens enucleated as a primary treatment or after conservative treatment and to correlate this expression with histopathological tumor features.

METHODS. Retrospective analysis was performed on retinoblastoma specimens obtained consecutively between 1993 and 2003 by enucleation either as primary treatment (group I) or after the failure of conservative treatment (group II). Sections from the formalin-fixed, paraffin-embedded specimens were stained with hematoxylin and eosin. Group I tumor differentiation was classified according to the percentage of Flexner-Wintersteiner rosettes. Group II tumors, categorized as viable-appearing, regressed with a well-differentiated component (WDC), and regressed. Other features, such as choroidal and optic nerve invasion, were evaluated. P-gp expression was graded semiquantitatively as negative, low, or high. Variables were statistically analyzed by ² and Student’s t-tests.

RESULTS. Histopathological assessment of group I revealed 65% moderately differentiated tumors, 30% well differentiated, and 5% poorly differentiated. Fifteen percent had optic nerve tumor invasion only, 20% choroidal invasion only, and 55% both choroidal and optic nerve invasion. Group II had 62.5% well-differentiated, regressed tumors; 25% had regressed tumors replaced by glial scarring; and 12.5% had tumors containing viable, poorly differentiated cells. Approximately 18% had choroidal tumor invasion only, 6.3% optic nerve tumor invasion only, and 6.3% simultaneous optic nerve and choroidal invasion. P-gp expression was observed in 60% of group I and 66.6% of group II. All P-gp-positive cases in group II had a high expression. P-gp was also expressed by 81.2% of well-differentiated tumors.

CONCLUSIONS. P-gp was expressed more frequently by well-differentiated retinoblastomas, especially those treated by chemotherapy before enucleation. This finding could be related to treatment failure.

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