[The prognostic significance of P-glycoprotein in children with acute lymphoblastic leukemia and neuroblastoma].
P-glycoprotein (P-gp), a pump located in the cell membrane, extrudes several clinically important drugs from the cell, and hence causes multidrug resistance (MDR). Reversing MDR is possible by using agents that inhibit the activity of P-gp. In this study, we tried to elucidate the prognostic relevance of P-gp in childhood acute lymphoblastic leukemia (ALL) and neuroblastoma. In a first prospective study in childhood ALL, an immunocytochemical APAAP assay was applied. Children scoring positive had a significantly worse outcome than those with a negative test result. In a second prospective study, the prognostic relevance of P-gp was confirmed, using the combination of immunocytochemistry and a functional flow cytometric assay. The combination of immunocytochemistry with the flow cytometric functional assay is being promoted as the most sensitive and clinically relevant amongst the different techniques. In neuroblastoma, ganglioneuroblastoma and ganglioneuroma, P-gp is detected by different assays: immunocytochemistry, flow cytometric immunological and functional tests and an in vivo imaging technique using 99mTc sestamibi. Immunocytochemistry alone did not provide a prognostic role for P-gp in neuroblastoma. On the contrary, using flow cytometric tests, many neuroblastomas scored positive and a discordance was found between the expression and activity of P-gp. P-gp was found more frequently in low-stage neuroblastoma, differentiated tumours and tumours after chemotherapy. A good correlation between flow cytometric results and imaging results was seen. Consequently, 99mTc sestamibi scintigraphy is not useful as an in vivo predictor of MDR in neuroblastoma. Unlike the findings in childhood ALL, P-gp does not contribute to MDR in neuroblastoma but seems to be a marker of differentiation.
De Moerloose
B
B
UZ Gent, Kliniek voor Kinderziekten C. Hooft, Afdeling pediatrische hematologie/oncologie, Faculteit Geneeskunde en Gezondheidswetenschappen--UGent, De Pintelaan 185--B 9000 Gent.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002648:Child; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1