Expression of the MDR1 gene product P-glycoprotein in childhood neuroblastoma.
BACKGROUND
In cancer treated with chemotherapy, multidrug resistance is characterized by increased genetic expression of P-glycoprotein (P-gp), which acts as an ATP-dependent drug-efflux pump. However, the clinical significance of the expression of the multidrug resistance gene (MDR1) product P-gp in neuroblastoma (NB) is still a matter of debate. In this study, the role of the expression of P-gp in NB was evaluated.


METHODS
NB tumor imprints and NB positive bone marrow smears from 23 children before and after multidrug chemotherapy were examined for P-gp expression by antialkaline phosphatase immunocytochemical analysis.


RESULTS
Before chemotherapy, only 10% of the NB samples showed positivity for P-gp. At diagnosis, no difference in P-gp expression was found between primary tumor cells and NB cells from metastases to bone marrow. P-gp positivity was only observed in patients with nonlocalized disease. P-gp positivity was never found in tumor cells that were histologically well differentiated. No clear correlation of P-gp positivity with poor prognostic parameters, such as chromosome 1p deletion or MYCN amplification, were found. Multidrug chemotherapy did not induce enhanced expression of P-gp in the neuroblasts. However, at clinical recurrence, P-gp expression was found in the metastatic NB cells of five of seven bone marrow samples examined.


CONCLUSIONS
The prognostic relevance of P-gp expression in NB was not clear from the results of this study. To resolve the uncertainties, a standardization of the methodology and more prospective studies are needed to determine whether routine analysis of P-gp is worth adding to the other prognostic parameters that are evaluated in NB patients. The finding that metastatic cells are capable of expressing MDR1, in contrast to the NB cells of the primary tumor, would certainly be an interesting topic for further study as work directed at understanding the progression to metastasis continues.
Dhooge
C R
CR
Department of Pediatric Hemato-Oncology, University Hospital of Gent, Belgium.
De Moerloose
B M
BM
Benoit
Y C
YC
Van Roy
N
N
Philippé
Laureys
G G
GG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019046:Bone Marrow Neoplasms / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019450:Genes, MDR; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D011003:Ploidies; D011379:Prognosis; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1