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Gain of chromosome 7 by chromogenic in situ hybridization (CISH) in chordomas is correlated to c-MET expression

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

Chordomas are low to intermediate grade malignancies that arise from remnants of embryonic notochord. They often recur after surgery and are highly resistant to conventional adjuvant therapies. Recently, the development of effective targeted molecular therapy has been investigated in chordomas that show receptors for tyrosine kinase (RTKs) activation. Expression of specific RTKs such as Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial transition factor (c-MET) in chordomas may offer valuable therapeutic options. We investigated changes in copy number of chromosome 7 and correlated it with EGFR gene status and EGFR and c-MET protein expression in 22 chordoma samples. Chromosome 7 copy number was evaluated by chromogenic in situ hybridization (CISH) and protein expression of EGFR and c-MET by immunohistochemistry. Tumors mostly showed conventional histopathologic features and were found mainly in sacral (41%) and cranial sites (54.5%). Aneusomy of chromosome 7 was seen in 73% of the samples, 62% of primary tumors and in all recurrent chordomas. EGFR and c-MET were both expressed, but only c-MET protein expression was significantly correlated with chromosome 7 aneusomy (P ≤ 0.001). c-MET overexpression may represent an early chromosome 7 alteration that could play an important role during chordoma pathogenesis. c-MET overexpression shows promise as a molecular marker of response to targeted molecular therapy in the treatment of chordomas.

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Abbreviations

CISH:

Chromogenic in situ hybridization

RTKs:

Receptors tyrosine kinase

EGFR:

Epidermal growth factor receptor

c-Met:

Mesenchymal-epithelial transition factor

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Acknowledgment

Maria Begnami work was supported by a grant 453399/2008-8 from CNPQ/Brazil.

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Authors and Affiliations

  1. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10-Magnuson CC, Room 2A10. 10 Center Drive, Bethesda, MD, 20892, USA

    Beatriz A. Walter, Vladimir A. Valera & Martha Quezado

  2. Department of Pathology, Hospital AC Camargo, São Paulo, Brazil

    Maria Begnami

  3. Department of Pathology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Mariarita Santi

  4. Department of Neuropathology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA

    Elisabeth J. Rushing

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  1. Beatriz A. Walter
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  2. Maria Begnami
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  3. Vladimir A. Valera
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  4. Mariarita Santi
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  5. Elisabeth J. Rushing
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  6. Martha Quezado
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Correspondence to Martha Quezado.

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Walter, B.A., Begnami, M., Valera, V.A. et al. Gain of chromosome 7 by chromogenic in situ hybridization (CISH) in chordomas is correlated to c-MET expression. J Neurooncol 101, 199–206 (2011). https://doi.org/10.1007/s11060-010-0250-5

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  • DOI: https://doi.org/10.1007/s11060-010-0250-5

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