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MET overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no MET activation through sarcoma-specific gene fusions

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Tumor Biology

Abstract

Overexpression of MET and polysomy 7 was formerly demonstrated in chordomas. We investigated mesenchymal-epithelial transition factor (MET) protein expression and copy numbers of chromosome 7 in human chordomas. Furthermore, tumors were screened for gene fusions (PAX3-FKHR, ASPL-TFE3, and SYT-SSX) previously shown to be associated with MET activation in sarcomas. Tissue microarrays (TMAs) were constructed from 66 chordoma samples. MET protein expression was assessed by immunohistochemistry using an immunoreactive score (IRS, scores 0–12). fluorescence in situ hybridization (FISH) with a dual-color DNA probe (7q31) for MET amplification was performed on TMA sections and RT-PCR for PAX3-FKHR, ASPL-TFE3 (type 1 + 2), and SYT-SSX (type 1 + 2) gene fusions on punch biopsies. All tumors (n = 66) expressed MET protein. FISH analysis of 33 tumors lacked MET gene amplification but showed polysomy of chromosome 7 in 15 (45.5%) tumors (13 low and two high polysomies). Although, polysomy 7 showed an increasing incidence with escalating MET IRS, this finding was not statistically significant. PAX3-FKHR, ASPL-TFE3, or SYT-SSX gene fusions were not demonstrable (n = 52). We found MET protein expression in all chordomas. A clear influence of polysomy 7 on MET protein expression could not be statistically demonstrated for this cohort. Moreover, gene fusions with the ability to cause MET overexpression do not occur in chordomas.

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Acknowledgments

This study was supported by grants from the IFORES-program of the Faculty of Medicine of the University of Duisburg-Essen (IFORES 107-20360 to F. G.).

The authors wish to acknowledge the excellent and enthusiastic technical assistance of Nicole Cramer, Gabriele Ladwig, and Andrea Kutritz.

The authors certify that there is no actual or potential conflict of interest in relation to this article.

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Authors and Affiliations

  1. Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany

    Florian Grabellus, Margarethe J. Konik, Karl Worm, Sien-Yi Sheu, Johannes A. P. van de Nes, Rupert Egensperger & Kurt W. Schmid

  2. Department of Internal Medicine and Cancer Research, University Hospital of Essen, University of Duisburg-Essen, 45122, Essen, Germany

    Sebastian Bauer

  3. Institute of Neuropathology, University Hospital Münster, 48149, Münster, Germany

    Werner Paulus

  4. Center of Neuropathology and Prion Research, Ludwig-Maximilians-University of München, 81377, München, Germany

    Rupert Egensperger

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  1. Florian Grabellus
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Correspondence to Florian Grabellus.

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Grabellus, F., Konik, M.J., Worm, K. et al. MET overexpressing chordomas frequently exhibit polysomy of chromosome 7 but no MET activation through sarcoma-specific gene fusions. Tumor Biol. 31, 157–163 (2010). https://doi.org/10.1007/s13277-010-0021-0

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  • DOI: https://doi.org/10.1007/s13277-010-0021-0

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