Research Papers:

This article has been corrected. Correction in: Oncotarget. 2017; 8:64652.

Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients

Lourdes Hontecillas-Prieto _, Daniel J. Garcia-Dominguez, Diego Pascual Vaca, Rosa Garcia-Mejias, David Marcilla, Gema L. Ramirez-Villar, Carmen Saez and Enrique de Álava

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Oncotarget. 2017; 8:11173-11186. https://doi.org/10.18632/oncotarget.14491

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Lourdes Hontecillas-Prieto1,*, Daniel J. Garcia-Dominguez1,*, Diego Pascual Vaca2, Rosa Garcia-Mejias1, David Marcilla2, Gema L. Ramirez-Villar3, Carmen Saez1,2,#, Enrique de Álava1,2,#

1Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

2Pathology Unit, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

3Pediatric Oncology Unit, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain

*These authors contributed equally to this work as first authors

#These authors contributed equally to this work as senior authors

Correspondence to:

Lourdes Hontecillas-Prieto, email: [email protected]

Daniel J. Garcia-Dominguez, email: [email protected]

Enrique de Álava, email: [email protected]

Carmen Saez, email: [email protected]

Keywords: Wilms tumours, multidrug resistance transporters, MDR3, MRP1, blastemal stratification

Received: October 11, 2016     Accepted: December 26, 2016     Published: January 04, 2017


Wilms tumour (WT) is the most common renal tumour in children. Most WT patients respond to chemotherapy, but subsets of tumours develop resistance to chemotherapeutic agents, which is a major obstacle in their successful treatment. Multidrug resistance transporters play a crucial role in the development of resistance in cancer due to the efflux of anticancer agents out of cells. The aim of this study was to explore several human multidrug resistance transporters in 46 WT and 40 non-neoplastic control tissues (normal kidney) from patients selected after chemotherapy treatment SIOP 93–01, SIOP 2001. Our data showed that the majority of the studied multidrug resistance transporters were downregulated or unchanged between tumours and control tissues. However, BCRP1, MDR3 and MRP1 were upregulated in tumours versus control tissues. MDR3 and MRP1 overexpression correlated with high-risk tumours (SIOP classification) (p = 0.0022 and p < 0.0001, respectively) and the time of disease-free survival was significantly shorter in patients with high transcript levels of MDR3 (p = 0.0359). MDR3 and MRP1 play a role in drug resistance in WT treatment, probably by alteration of an unspecific drug excretion system. Besides, within the blastemal subtype, we observed patients with low MDR3 expression were significantly associated with a better outcome than patients with high MDR3 expression. We could define two types of blastemal WT associated with different disease outcomes, enabling the stratification of blastemal WT patients based on the expression levels of the multidrug resistance transporter MDR3.

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