Increased expression of multidrug resistance-associated genes after chemotherapy in pediatric solid malignancies.
OBJECTIVE
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.
Oue
Takaharu
T
Division of Pediatric Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. ooue@pedsurg.med.osaka-u.ac.jp
Yoneda
Akihiro
A
Uehara
Shuichiro
S
Yamanaka
Hiroaki
H
Fukuzawa
Masahiro
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1