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.

journal_name

Cancer

journal_title

Cancer

authors

Komdeur R,Klunder J,van der Graaf WT,van den Berg E,de Bont ES,Hoekstra HJ,Molenaar WM

doi

10.1002/cncr.11259

subject

Has Abstract

pub_date

2003-04-15 00:00:00

pages

1999-2005

issue

8

eissn

0008-543X

issn

1097-0142

journal_volume

97

pub_type

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