Subject(s)
Airway Management/instrumentation , Airway Management/methods , Cardiopulmonary Resuscitation , Laryngoscopes , Manikins , Adult , Equipment Design , Female , Humans , Male , Time FactorsABSTRACT
PURPOSE: To compare the expression of pregnane xenobiotic receptor and certain multi-drug resistance proteins in retinoblastoma. METHODS: Using tissue microarray analyses, we studied 62 pathology specimens for expression of pregnane xenobiotic receptor, multi-drug resistance 1/P glycoprotein, multi-drug resistance proteins 1, 2, and 4, and breast cancer resistant protein. RESULTS: Comparing tumors treated with primary enucleation with tumors treated with chemotherapy and/or radiation showed no significant differences in the expression of multi-drug resistance proteins or pregnane xenobiotic receptor. Pregnane xenobiotic receptor was correlated with multi-drug resistance protein 2 expression (p < 0.001). CONCLUSION: Our results indicate selection, rather than induction, of chemoresistant cells as a cause for treatment failure in managing retinoblastoma with primary systemic chemotherapy.
Subject(s)
Multidrug Resistance-Associated Proteins/metabolism , Receptors, Steroid/metabolism , Retinal Neoplasms/metabolism , Retinoblastoma/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/metabolism , Child , Cohort Studies , Drug Therapy , Eye Enucleation , Gene Expression , Humans , Microarray Analysis , Multidrug Resistance-Associated Protein 2 , Neoplasm Proteins/metabolism , Pregnane X Receptor , Radiotherapy , Retinal Neoplasms/therapy , Retinoblastoma/therapyABSTRACT
PURPOSE: To compare the expression of multidrug-resistant 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 had undergone primary enucleation. A histologic specimen from each patient was retrieved from the pathology archives and a tissue gene microarray was constructed (0.6 x 3-4 mm). Standard immunohistochemical techniques were used to study the tissue microarrays for the expression of the ATP-binding cassette (ABC) transporters: breast cancer resistance protein (BCRP; ABCG2), multidrug-resistant protein 1/P-glycoprotein (MDR1/Pgp; ABCB1), multidrug-resistant-associated protein 1 (MRP1; ABCC1), MRP2 (ABCC2), and MRP4 (ABCC4). RESULTS: Of the 18 specimens retrieved, 16 had adequate tissue for study. MRP1 was expressed in 8 (50%) of 16 tumors, and MRP2 was expressed in 5 (31%) of 16 tumors. MDR1/Pgp was found in 2 (12%) of 16 retinoblastomas. MRP4 and BCRP were not detected in any of the tumors studied. CONCLUSIONS: The results show that multiple ABC transporters were present in a cohort of sporadic patients with unilateral retinoblastoma who underwent primary enucleation. Studies are planned of the expression of ABC transporters in eyes treated by chemotherapy and/or radiation as a comparison with this group.
