EXPRESSION OF MDR1 P-GLYCOPROTEIN AND P110 IN NEUROBLASTOMA/

Overexpression of the multidrug resistance gene, mdr1, and its product , P-glycoprotein (Pgp), has been associated with cross-resistance to s tructurally unrelated compounds in cell lines and tumours. Recently, a non-Pgp-mediated form of drug resistance has been described, due to t he overexpression of p110, a transport protein. Thirty formalin-fixed, paraffin-embedded neuroblastoma samples from 21 cases were examined f or overexpression of mdr1 and Pgp using newly established non-radioact ive in situ hybridization and sensitive immunocytochemical techniques. Tumours were examined from patients with all the stages of disease an d from primary and metastatic sites. Paired tumour samples (pre-chemot herapy and post-chemotherapy) were available from cases with stage 2 ( n=1) and stage 4 disease (n=8). Immunoreactivity to p110 was also test ed on all the samples. Mdr1 mRNA was expressed in 16/21 cases and in a ll the stages. Pgp immunoreactivity was detected in all the cases. Wea k cytoplasmic immunoreactivity to p110 was seen in the ganglion cells in 12/21 cases. The expression of mdr1, Pgp, and p110 showed a statist ically significant (two-sided Fisher exact test, P=0.04, 0.03, 0.04, r espectively) correlation with differentiation (Beckwith and Martin gra ding) but there was no correlation with survival. Pgp immunoreactivity also showed a significant correlation with favourable clinical variab les: age less than 1 year at diagnosis and stages 1, 2, and 4s (two-si ded Fisher exact test, P=0.01, 0.005, respectively).