THE PROGNOSTIC VALUE OF MDR1 GENE-EXPRESSION IN PRIMARY UNTREATED NEUROBLASTOMA

The contribution of MDR1 gene expression to the biology of childhood n euroblastoma is unclear. To clarify the role of MDR1 in this malignanc y, we examined the relationship between MDR1 expression and patient ou tcome in subsets of 60 primary untreated neuroblastomas for which MYCN gene copy number and expression of the multidrug resistance-associate d-protein (MRP) gene had been previously characterised. In contrast to MRP gene expression, MDR1 expression was lower in tumours with MYCN g ene amplification compared with those without amplification. Strong co rrelations between MDR1 and MRP gene expression, and between MDR1 and MYCN gene expression, were observed in tumours lacking MYCN gene ampli fication (P<0.0005). In these single-copy tumours, very high MDR1 gene expression was significantly associated with poor outcome (P<0.05). V ery high MDR1 expression was also strongly predictive of poor outcome in older children (P<0.0001), but not in infants. These findings sugge st a clinical role for the MDR1 gene in specific subgroups of primary neuroblastoma. (C) 1997 Elsevier Science Ltd.