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Multidrug-Resistance P-Glycoprotein Expression in Tumor Cells and Intratumoral Capillary Endothelial Cells

Francesca Diomedi Camassei MD, Giuseppe Arancia MD, Maurizio Cianfriglia MD, Cesare Bosman MD, Paola Francalanci MD, Lucilla Ravà PhD, Alessandro Jenkner MD, Alberto Donfrancesco MD, Renata Boldrini MD
DOI: http://dx.doi.org/10.1309/L44X-L5DN-1VHV-X30N 484-490 First published online: 1 March 2002


The development of chemoresistance in a variety of cancers seems related to overexpression of the P-glycoprotein (P-gp) drug pump. Nephroblastoma, the most common malignant renal tumor of childhood, usually is responsive to treatment, and prognosis is favorable in most cases. However, the disease in a subset of patients is refractory to treatment, and the disease follows an aggressive course.

To study P-gp expression in this tumor and its correlation with outcome, tumor samples from 93 patients were examined by immunohistochemical analysis. P-gp expression was determined separately in both tumor cells and intratumoral capillary endothelium. The likelihood ratio test, the Kaplan-Meier method, and the log-rank test were used to evaluate its association with clinical course, grade, stage, and administration of preoperative chemotherapy.

The results for the majority of nephroblastomas were variably positive; in 43 (46%) of them, newly formed capillary endothelial cells also stained positive. While no association of P-gp expression in tumor cells with clinical course, stage, and grade could be demonstrated, positivity in endothelial cells correlated significantly with unfavorable outcome, suggesting that chemoresistance depended on an active blood-tumor barrier. Previous chemotherapy induced P-gp overexpression in tumor cells.

Key Words:
  • P-glycoprotein
  • Nephroblastoma
  • Intratumoral capillary endothelial cells
  • Chemoresistance
  • Immunohistochemistry