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Doublecortin is preferentially expressed in invasive human brain tumors

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Abstract

Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular zone and dentate gyrus were used as positive controls for immunostaining, and specificity of antibody staining was demonstrated by peptide neutralization. DCX was highly expressed in both high-grade invasive tumors (glioblastoma, n=11; anaplastic astrocytoma/oligoastrocytoma, n=7; and medulloblastoma/PNET, n=6) and low-grade invasive tumors (oligodendroglioma, n=3; and astrocytoma/oligoastrocytoma, n=5). However, DCX was less intensely expressed in the circumscribed group of tumors (pilocytic astrocytoma, n=6; ependymoma/subependymoma, n=7; dysembryoplastic neuroepithelial tumor, n=4; ganglioglioma, n=2; meningioma, n=9; and schwannoma, n=9). By the Cochran-Mantel-Haenszel statistical test, the circumscribed group was significantly different from both the high-grade invasive group (P<0.0001) and the low-grade invasive group (P<0.0001). We conclude that DCX is preferentially expressed in invasive brain tumors. In addition, DCX immunostaining was stronger at the margin of the tumor than at the center. For a subset of these tumors, we also detected DCX mRNA and protein by Northern and Western blotting. DCX mRNA and protein was detected in glioma cell lines by Northern blotting, immunofluorescence microscopy and Western blotting. Collectively, the immunohistochemistry, Western blots and Northern blots conclusively demonstrate expression of DCX by human brain tumors.

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Acknowledgements

We thank Li Li for her discussions of her studies of DCX expression in neural precursor cells and Qin Liu for her help with the statistical analyses. This study was supported by NIH grants CA-10737 and NS-21716 to AHR.

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Author notes

  1. N. Scott Litofsky

    Present address: Division of Neurological Surgery, University of Missouri-Columbia School of Medicine, Columbia, Missouri, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Room 819, Worcester, MA, 01605, USA

    Marie-Claire Daou & Alonzo H. Ross

  2. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Thomas W. Smith

  3. Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    N. Scott Litofsky

  4. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Chung C. Hsieh

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  1. Marie-Claire Daou
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Correspondence to Alonzo H. Ross.

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Daou, MC., Smith, T.W., Litofsky, N.S. et al. Doublecortin is preferentially expressed in invasive human brain tumors. Acta Neuropathol 110, 472–480 (2005). https://doi.org/10.1007/s00401-005-1070-0

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