High levels of MRP gene expression in patients with neuroblastoma correlate strongly with poor outcome. The findings suggest that expression of this multidrug-resistance gene accounts for the association between N-myc amplification and reduced survival.
The results of this prospective study confirm our earlier findings and support a clinically relevant role for MRP1 gene expression in neuroblastoma. These findings have implications for the biology, prognosis, and treatment of this disease and provide evidence that MRP1 is a bone fide molecular target for reversing chemotherapy resistance in aggressive drug-refractory neuroblastoma.
High MYCN gene expression is strongly predictive of poor outcome in older children with neuroblastoma, but not in infants. The findings help explain the controversy in the literature about the prognostic value of MYCN gene expression and highlight the different biology of neuroblastoma that presents in infants and older children.
The differential diagnosis of neuroblastoma from other small round-cell tumors of childhood , although clinically of great importance , is sometimes difficult due to the almost indistinguishable appearance of such tumors by conventional microscopy. Because neuroblastomas are characterized by the synthesis of catecholamines , we investigated the possibility that expression of genes involved in this pathway could serve as a molecular marker for this disease. A reverse transcriptase polymerase chain reaction assay was used to analyze expression of tyrosine hydroxylase and dopa decarboxylase in 84 pediatric malignancies including 55 neuroblastomas , 6 Ewing's sarcomas/ primitive neuroectodermal tumors , 7 lymphomas, 6 leukemias , 2 rhabdomyosarcomas , 6 osteosarcomas, and 2 phaeochromocytomas. Of the 55 neuroblastoma samples analyzed , 54 expressed clearly detectable levels of both genes. The one sample that did not express either of the genes was rediagnosed both clinically and by molecular genetic analysis as a Ewing's sarcoma. Of the 29 non-neuroblastoma tumor samples examined , the only tumor samples that expressed clearly detectable levels of both tyrosine hydroxylase and dopa decarboxylase were phaeochromocytomas. Like neuroblastomas , these tumors are characterized by high levels of catecholamines. These findings suggest that expression of genes involved in catecholamine biosynthesis may be useful for differentiating neuroblastoma from other small round-cell tumors of childhood. (Am J Pathol 1999, 155:17-21)
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