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 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, 0.005, respectively).