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American Journal of Pathology, Vol 139, 305-315, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Expression of mdr-1/P-glycoprotein in human neuroblastoma

SE Bates, CY Shieh and M Tsokos
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Increased expression of the mdr-1 gene encoding the drug efflux pump P- glycoprotein is a well-established mediator of acquired drug resistance in vitro, and a similar role has been hypothesized in vivo in human malignancy. Because expression of mdr-1 is increased in neuroblastoma cell lines by differentiating agents, the authors hypothesized a similar correlation with differentiation in vivo in neuroblastomas. In 12 tumors from 11 patients, total RNA analysis demonstrated no correlation with differentiation, but a correlation could be detected in the cell-based methods of analysis. The very primitive 'stroma'- poor, poorly differentiated neuroblastomas had low levels of mdr-1/P- glycoprotein. The intermediate grades had higher levels of expression and although heterogeneity of differentiation appeared within these tumors, both primitive and more differentiated cells expressed the gene at comparable levels within the tumor. One very well-differentiated neuroblastoma, a ganglioneuroma, had no detectable expression in the neurofibrillary material, but demonstrated expression in adjacent large ganglionic cells. Thus mdr-1/P-glycoprotein expression increased with increasing differentiation among tumors, and was present in ganglionic cells in the most well-differentiated tumor. The three tumors with the highest levels of expression were obtained from patients who received preoperative chemotherapy.


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J. M. Maris and K. K. Matthay
Molecular Biology of Neuroblastoma
J. Clin. Oncol., July 1, 1999; 17(7): 2264 - 2264.
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Copyright © 1991 by the American Society for Investigative Pathology.