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).
Ramani
P
P
Department of Histopathology, Hospital for Children NHS Trust, London, U.K.
Dewchand
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000911:Antibodies, Monoclonal; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D018305:Ganglioneuroblastoma / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D009447:Neuroblastoma / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D012333:RNA, Messenger