Increased expression of multidrug resistance–associated genes after chemotherapy in pediatric solid malignancies

Abstract

Background/Purpose The overexpression of multidrug resistance (MDR)–associated genes in primary untreated tumors has been proven to be associated with worse prognosis in various pediatric malignancies. This study compared the expression of 3 MDR-associated genes, MDR1, MDR-associated protein 1 ( MRP1), and lung resistance–related protein ( LRP), in pediatric tumors before and after chemotherapy to elucidate the mechanism of MDR during chemotherapy. Methods Surgical specimens of both primary and chemotherapy-treated tumors were obtained from 24 patients with pediatric malignancies (neuroblastoma [NB] 8; hepatoblastoma [HB] 8; Wilms tumor [WT] 4; rhabdomyosarcoma [RB] 4). The expression of MDR1, MRP1, and LRP was evaluated using the immunohistochemical staining. Results In primary tumors, MDR1 expression was observed in 6 NBs, 8 HBs, 3 WTs, and 3 RBs. MRP1 expression was observed in 3 NBs and 1 HB. LRP expression was not detected in any of the primary tumors. After chemotherapy, MDR1 expression was observed to increase in 5 NBs, 4 HBs, 2 WTs, and 3 RBs. MRP1 expression was newly observed or increased in 7 NBs, 4 HBs, and 3 RBs. LRP expression was newly observed in 3 HBs and 2 WTs. Conclusions These results indicate that these 3 MDR-associated genes were upregulated after chemotherapy in various pediatric malignancies. These findings may be useful to understand the mechanism of drug resistance in pediatric malignancies.