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Quantitative PCR analysis of the expression profile of genes related to multiple drug resistance in tumors of the central nervous system

  • Lab. Investigation - human/animal tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Objectives

To evaluate and compare the profile of expression of genes related to drug resistance in brain tumors and to analyze the impact of the increased expression of these genes on overall survival.

Methods

Eighty microdissected brain tumor samples from 79 patients were analyzed by RQ-PCR for the genes MDR1, MRP1, MRP3, LRP and BCRP. Protein expression was assessed by immunohistochemistry for MRP1 and LRP genes. Pediatric cases (0 to 20 years): 46 (17F:29M, median age 7.3 ± 5.9 years); adult tumors: 33 (17F:16M, median age 46.6 ± 14.5 years). Histological diagnoses: 21 astrocytomas I and II, 28 astrocytomas III and glioblastomas, 17 medulloblastomas, 8 ependymomas, and 6 oligodendrogliomas.

Results

glial tumors expressed higher MDR1 (P = 0.003) and BCRP (P = 0.03) levels than embryonic tumors. Low-grade astrocytomas expressed high MDR1 (P = 0.001), MRP3 (P = 0.01) and LRP (P = 0.02) levels. The MRP1 gene was preferentially expressed by medulloblastomas (P = 0.04) and ependymomas (P = 0.04); ependymomas also presented an increase of LRP (P = 0.02). The mRNA levels of MRP1 and LRP genes were associated to protein expression. The profile of gene expression of primary pilocytic astrocytomas of the hypothalamus and of the other locations was similar. Increased expression of resistance genes, separately or jointly, was not correlated with shorter overall survival in patients with medulloblastomas/PNET and malignant gliomas.

Conclusions

Drug resistance genes do not explain the higher sensitivity of gliomas of the hypothalamus/pituitary/optic pathways to chemotherapy. The increased expression of resistance genes had no impact on the overall survival of patients with medulloblastomas/PNET and high grade gliomas. High MDR1, MRP3 and LRP levels may be implicated in the primary resistance of pilocytic astrocytomas to chemotherapy.

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Acknowledgements

We would like to thank Dr Eduardo Rego, Dr Lorena Figueiredo-Pontes and Aglair Garcia, from the Hematology Department, that kindly provided us the IH antibodies. We also thank Dr Roberto Silva Costa, Dr Luciano Neder, Dr Daniel Brandão and Ana Maria Anselmi Dorigan, from the Pathology Department, for performing and interpreting the IH assays.

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Authors and Affiliations

  1. Discipline of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 7 andar. Av. Bandeirantes, 3900. Bairro Monte Alegre, Ribeirão Preto, SP, CEP 14048-900, Brazil

    Elvis Terci Valera, Agda Karina Brodoloni Lucio-Eterovic, Carlos Alberto Scrideli, Rosane Gomes de Paula Queiroz, Fabio José do Nascimento Motta & Luiz Gonzaga Tone

  2. Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

    Luciano Neder

  3. Discipline of Neurosurgery, Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

    Helio Rubens Machado & Carlos Gilberto Carlotti-Junior

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  1. Elvis Terci Valera
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  2. Agda Karina Brodoloni Lucio-Eterovic
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Correspondence to Elvis Terci Valera.

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Valera, E.T., Lucio-Eterovic, A.K.B., Neder, L. et al. Quantitative PCR analysis of the expression profile of genes related to multiple drug resistance in tumors of the central nervous system. J Neurooncol 85, 1–10 (2007). https://doi.org/10.1007/s11060-007-9382-7

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  • DOI: https://doi.org/10.1007/s11060-007-9382-7

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