Publication

Multidrug resistance proteins in rhabdomyosarcomas - Comparison between children and adults

Komdeur, R., Klunder, J., van der Graaf, WTA., van den Berg, E., de Bont, ESJM., Hoekstra, HJ. & Molenaar, WM., 15-Apr-2003, In : Cancer. 97, 8, p. 1999-2005 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • R Komdeur
  • J Klunder
  • WTA van der Graaf
  • E van den Berg
  • ESJM de Bont
  • HJ Hoekstra
  • WM Molenaar

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 2 embryonal or botryoid RMS. Among the adults, there were 10 embryonal, 3 alveolar, and 3 pleomorphic RMS. Samples were scored as negative or positive 3 according to the percentage of immunoreactive tumor cells: 0.5 (1-5%), 1 (5-25%), 2 (26-50%), 3 (51-75%), or 4 (>75%). 4

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. (C) 2003 American Cancer Society.

Original languageEnglish
Pages (from-to)1999-2005
Number of pages7
JournalCancer
Volume97
Issue number8
Publication statusPublished - 15-Apr-2003

    Keywords

  • rhabdomyosarcoma, age, P-glycoprotein, multidrug resistance-associated protein 1, lung resistance-related protein, CARCINOMA SW-620 CELLS, INTERGROUP RHABDOMYOSARCOMA, P-GLYCOPROTEIN, DRUG-RESISTANCE, ALVEOLAR RHABDOMYOSARCOMA, PEDIATRIC RHABDOMYOSARCOMA, CHILDHOOD RHABDOMYOSARCOMA, GENE FUSIONS, CLASSIFICATION, SARCOMAS

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