title: Multidrug resistance proteins in rhabdomyosarcomas: comparison between children and adults.
abstract: BACKGROUND
  Pediatric rhabdomyosarcomas (RMS) have a more advantageous prognosis after multimodality treatment compared with adult RMS, which might be related to a decreased sensitivity to chemotherapy in adults. Resistance to chemotherapy might be conveyed by the multidrug resistance (MDR)-associated proteins P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and lung resistance-related protein (LRP). It was therefore suggested that these proteins were expressed differently in pediatric and adult patients.
  
  
  METHODS
  The expression of P-gp, MRP1, and LRP was assessed immunohistochemically in 45 specimens of untreated RMS: 29 were obtained from children younger than 16 years old and 16 were obtained from adults. All children had an embryonal or botryoid RMS. Among the adults, there were 10 embryonal, 3 alveolar, and 3 pleomorphic RMS. Samples were scored as negative or positive according to the percentage of immunoreactive tumor cells: 0.5 (1-5%), 1 (5-25%), 2 (26-50%), 3 (51-75%), or 4 (> 75%).
  
  
  RESULTS
  Expression of LRP was more pronounced in embryonal and pleomorphic RMS in adults compared with RMS in children. In addition, LRP expression correlated with age at diagnosis. Alveolar RMS had remarkably low LRP expression. Expression of P-gp and MRP1 did not differ significantly between children and adults.
  
  
  CONCLUSIONS
  In this series of embryonal and pleomorphic RMS, an increased LRP expression was observed in adults, which may explain their worse response to chemotherapy reported in other studies. In alveolar RMS, a low LRP expression was observed, suggesting that other mechanisms are responsible for the resistant phenotype in most of these tumors.
authors.affiliation: Department of Surgical Oncology, University Hospital Groningen, Groningen, The Netherlands.
authors.forename: Rudy
authors.initials: R
authors.lastname: Komdeur
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klunder
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: Eva
authors.initials: E
authors.lastname: van den Berg
authors.forename: Eveline S J M
authors.initials: ES
authors.lastname: de Bont
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Hoekstra
authors.forename: Willemina M
authors.initials: WM
authors.lastname: Molenaar
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1