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Multidrug resistance proteins in rhabdomyosarcomas
Author(s) -
Komdeur Rudy,
Klunder Jenneke,
van der Graaf Winette T. A.,
van den Berg Eva,
de Bont Eveline S. J. M.,
Hoekstra Harald J.,
Molenaar Willemina M.
Publication year - 2003
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.11259
Subject(s) - medicine , chemotherapy , multiple drug resistance , p glycoprotein , pathology , immunohistochemistry , oncology , drug resistance , biology , genetics
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. Cancer 2003;97:1999–2005. © 2003 American Cancer Society. DOI 10.1002/cncr.11259