Research Papers:

BCRP expression in schwannoma, plexiform neurofibroma and MPNST

Maurits de Vries _, Olaf van Tellingen, Andel. G.L. van der Mey, Antonius M.G. Bunt, Inge Briaire-de Bruijn and Pancras C.W. Hogendoorn

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Oncotarget. 2017; 8:88751-88759. https://doi.org/10.18632/oncotarget.21075

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Maurits de Vries1,2, Olaf van Tellingen3, Andel. G.L. van der Mey2, Antonius M.G. Bunt4, Inge Briaire-de Bruijn1 and Pancras C.W. Hogendoorn1

1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

2Department of Otolaryngology, Leiden University Medical Center, Leiden, The Netherlands

3Division of Pharmacology/Mouse Cancer Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands

4IzumiBiosciences, Inc., Lexington, USA

Correspondence to:

Maurits de Vries, email: [email protected]

Keywords: BCRP, schwannoma, neurofibroma, drug resistance, MPNST

Received: March 17, 2017     Accepted: June 17, 2017     Published: September 16, 2017


Background: peripheral nerve sheath tumors comprise a broad spectrum of neoplasms. Vestibular schwannomas and plexiform neurofibromas are symptomatic albeit benign, but a subset of the latter pre-malignant lesions will transform to malignant peripheral nerve sheath tumors (MPNST). Surgery and radiotherapy are the primary strategies to treat these tumors. Intrinsic resistance to drug therapy characterizes all three tumor subtypes. The breast cancer resistance protein BCRP is a transmembrane efflux transporter considered to play a key role in various biological barriers such as the blood brain barrier. At the same time it is associated with drug resistance in various tumors. Its potential role in drug resistant tumors of the peripheral nervous system is largely unknown.

Objective: to assess if BCRP is expressed in vestibular schwannomas, plexiform neurofibromas and MPNST.

Material and methods: immunohistochemical staining for BCRP was performed on a tissue microarray composed out of 22 vestibular schwannomas, 10 plexiform neurofibromas and 18 MPNSTs.

Results: sixteen out of twenty-two vestibular schwannomas (73%), nine out of ten plexiform neurofibromas (90%) and six out of eighteen MPNST (33%) expressed BCRP in the vasculature. Tumor cells were negative.

Conclusion: BCRP is present in the vasculature of vestibular schwannomas, plexiform neurofibromas and MPSNT. Therefore, it may reduce the drug exposure of underlying tumor tissues and potentially cause failure of drug therapy.

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