Multidrug Resistant Protein Expression in Untreated Retinoblastoma

Abstract

Abstract: : Purpose: To compare the expression of multidrug resistance proteins in retinoblastoma tumors among eyes treated with primary enucleation. Methods: A group of 18 patients with unilateral retinoblastoma with advanced intraocular disease was selected for the study. All patients underwent primary enucleation. A histological specimen for each patient was retrieved from the pathology archives and a tissue microarray was constructed (0.6 mm X 3–4 mm). Using standard immunohistochemical techniques, the tissue microarrays were studied for the expression of the ABC transporters: breast cancer resistance protein (BCRP; ABCG2), multidrug resistant protein 1 (MRP1; ABCC1), multidrug resistant protein 2 (MRP2; ABCC2), and multidrug resistant protein 4 (MRP4; ABCC4). Results: We noted that expression of MRP1 was unequivocally positive in 8/18 (44.4%) and 4/8 showed apical staining of rosettes. Weak focal staining was observed in 3/18 (16.7%). Normal retinal tissue was negative. MRP2 was not noted in any tumor, while the normal retinal pigment epithelium stained strongly positive. MRP4 demonstrated focal positive staining in 5/18 (27.8%), and when present normal retinal tissue was negative. BCRP showed strong focal positive staining in 5/18 (27.8%) and weak focal staining in 2/18 (11.1%). Normal retinal tissue stained positively when present. Interestingly, we found that three tumors were positive for BCRP and MRP1, two were positive for MRP1 and MRP4, and one was positive for BCRP and MRP4. Two tumors were positive for BCRP, MRP1, and MRP4. Conclusions: The results of our study show that multiple ABC transporters are present in a cohort of sporadic patients with unilateral retinoblastoma who underwent primary enucleation. Additional studies are ongoing to examine additional transporters, including P–glycoprotein (MDR1; ABCB1). Furthermore, we plan studies of the expression of ABC transporters in eyes treated as a comparison with this group.

Keywords: retinoblastoma • oncology • pharmacology