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Keywords:

  • Neuroblastoma;
  • multidrug resistance;
  • mdr1;
  • Pgp;
  • p110

Abstract

Overexpression of the multidrug resistance gene, mdr1, and its product, P-glycoprotein (Pgp), has been associated with cross-resistance to structurally unrelated compounds in cell lines and tumours. Recently, a non-Pgp-mediated form of drug resistance has been described, due to the overexpression of p110, a transport protein. Thirty formalin-fixed, paraffin-embedded neuroblastoma samples from 21 cases were examined for overexpression of mdr1 and Pgp using newly established non-radioactive in situ hybridization and sensitive immunocytochemical techniques. Tumours were examined from patients with all the stages of disease and from primary and metastatic sites. Paired tumour samples (pre-chemotherapy and post-chemotherapy) were available from cases with stage 2 (n=1) and stage 4 disease (n=8). Immunoreactivity to p110 was also tested on all the samples. Mdr1 mRNA was expressed in 16/21 cases and in all the stages. Pgp immunoreactivity was detected in all the cases. Weak cytoplasmic immunoreactivity to p110 was seen in the ganglion cells in 12/21 cases. The expression of mdr1, Pgp, and p110 showed a statistically significant (two-sided Fisher exact test, P=0.04, 0.03, 0.04, respectively) correlation with differentiation (Beckwith and Martin grading) but there was no correlation with survival. Pgp immunoreactivity also showed a significant correlation with favourable clinical variables: age less than 1 year at diagnosis and stages 1, 2, and 4 s (two-sided Fisher exact test, P=0.01, 0.05, respectively).