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Role of chemotherapy resistance genes in outcome of neuroblastoma
Author(s) -
de Cremoux Patricia,
JourdanDaSilva Nathalie,
Couturier Jérôme,
TranPerennou Carine,
Schleiermacher Gudrun,
Fehlbaum Pascale,
Doz François,
Mosseri Véronique,
Delattre Olivier,
Klijanienko Jerzy,
Vielh Philippe,
Michon Jean
Publication year - 2007
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.20853
Subject(s) - neuroblastoma , medicine , chemotherapy , disease , progressive disease , multiple drug resistance , oncology , gene , drug resistance , cancer research , biology , cell culture , genetics
Background Neuroblastoma is a heterogeneous pediatric disease. Most patients with localized disease usually have a favorable prognosis, but patients with advanced disease have a poor prognosis despite combination chemotherapy. Treatment failure may be attributable to resistance to cytotoxic drugs. Procedure Using quantitative RT‐PCR, we investigated the clinical significance of the level of mRNA expression of multidrug resistance genes (MDR1, MRP1, MRP5, LRP) in a series of 29 advanced neuroblastoma samples. Results At the end of induction chemotherapy, 48% of patients achieved a clinical complete response, 28% achieved a partial response or stable disease, and 24% presented progressive disease. MDR1 mRNA overexpression (i.e., mRNA level >2 copies of MDR1 gene) was observed in 74% of samples, and MRP1, MRP5, LRP overexpression was observed less frequently (30, 33, and 33% of samples, respectively). None of these parameters were predictive of response, relapse, or survival. However, clinical response to treatment was highly predictive of relapse‐free survival and overall survival. Conclusions High expression of these multidrug resistance genes in advanced neuroblastoma is not the main parameter of response to cytotoxic drugs; clinical response to treatment remains the most important parameter in predicting the prognosis of patients with advanced neuroblastoma, until other relevant laboratory parameters have been identified. Pediatr Blood Cancer 2007;48:311–317. © 2006 Wiley‐Liss, Inc.