Acta Neuropathologica

, Volume 125, Issue 5, pp 651–658 | Cite as

Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein

  • Leonille Schweizer
  • Christian Koelsche
  • Felix Sahm
  • Rosario M. Piro
  • David Capper
  • David E. Reuss
  • Stefan Pusch
  • Antje Habel
  • Jochen Meyer
  • Tanja Göck
  • David T. W. Jones
  • Christian Mawrin
  • Jens Schittenhelm
  • Albert Becker
  • Stephanie Heim
  • Matthias Simon
  • Christel Herold-Mende
  • Gunhild Mechtersheimer
  • Werner Paulus
  • Rainer König
  • Otmar D. Wiestler
  • Stefan M. Pfister
  • Andreas von Deimling
Original Paper

Abstract

Non-central nervous system hemangiopericytoma (HPC) and solitary fibrous tumor (SFT) are considered by pathologists as two variants of a single tumor entity now subsumed under the entity SFT. Recent detection of frequent NAB2-STAT6 fusions in both, HPC and SFT, provided additional support for this view. On the other hand, current neuropathological practice still distinguishes between HPC and SFT. The present study set out to identify genes involved in the formation of meningeal HPC. We performed exome sequencing and detected the NAB2-STAT6 fusion in DNA of 8/10 meningeal HPC thereby providing evidence of close relationship of these tumors with peripheral SFT. Due to the considerable effort required for exome sequencing, we sought to explore surrogate markers for the NAB2-STAT6 fusion protein. We adopted the Duolink proximity ligation assay and demonstrated the presence of NAB2-STAT6 fusion protein in 17/17 HPC and the absence in 15/15 meningiomas. More practical, presence of the NAB2-STAT6 fusion protein resulted in a strong nuclear signal in STAT6 immunohistochemistry. The nuclear reallocation of STAT6 was detected in 35/37 meningeal HPC and 25/25 meningeal SFT but not in 87 meningiomas representing the most important differential diagnosis. Tissues not harboring the NAB2-STAT6 fusion protein presented with nuclear expression of NAB2 and cytoplasmic expression of STAT6 proteins. In conclusion, we provide strong evidence for meningeal HPC and SFT to constitute variants of a single entity which is defined by NAB2-STAT6 fusion. In addition, we demonstrate that this fusion can be rapidly detected by STAT6 immunohistochemistry which shows a consistent nuclear reallocation. This immunohistochemical assay may prove valuable for the differentiation of HPC and SFT from other mesenchymal neoplasms.

Keywords

Solitary fibrous tumor SFT Hemangiopericytoma NAB2 STAT6 Fusion protein Meningioma Immunohistochemistry Proximity ligation 

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Leonille Schweizer
    • 1
    • 2
  • Christian Koelsche
    • 1
    • 2
  • Felix Sahm
    • 1
    • 2
  • Rosario M. Piro
    • 3
  • David Capper
    • 1
    • 2
  • David E. Reuss
    • 1
    • 2
  • Stefan Pusch
    • 2
  • Antje Habel
    • 1
  • Jochen Meyer
    • 2
  • Tanja Göck
    • 1
  • David T. W. Jones
    • 4
  • Christian Mawrin
    • 5
  • Jens Schittenhelm
    • 6
  • Albert Becker
    • 7
  • Stephanie Heim
    • 8
  • Matthias Simon
    • 9
  • Christel Herold-Mende
    • 10
  • Gunhild Mechtersheimer
    • 11
  • Werner Paulus
    • 8
  • Rainer König
    • 3
    • 12
    • 13
  • Otmar D. Wiestler
    • 14
  • Stefan M. Pfister
    • 4
    • 15
  • Andreas von Deimling
    • 1
    • 2
  1. 1.Department of NeuropathologyInstitute of Pathology, Ruprecht-Karls-University HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit NeuropathologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Division of Theoretical BioinformaticsGerman Cancer Research Center (DKFZ)HeidelbergGermany
  4. 4.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  5. 5.Department of NeuropathologyOtto Von Guericke University MagdeburgMagdeburgGermany
  6. 6.Department of NeuropathologyInstitute of Pathology and Neuropathology, University TübingenTübingenGermany
  7. 7.Department of NeuropathologyUniversity of BonnBonnGermany
  8. 8.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  9. 9.Department of NeurosurgeryUniversity of BonnBonnGermany
  10. 10.Department of NeurosurgeryUniversity Hospital HeidelbergHeidelbergGermany
  11. 11.Department of PathologyInstitute of Pathology, Ruprecht-Karls-University HeidelbergHeidelbergGermany
  12. 12.Center for Sepsis Control and CareUniversity Hospital JenaJenaGermany
  13. 13.Leibniz Institute for Natural Products Research and Infection Biology, Hans-Knöll InstituteJenaGermany
  14. 14.German Cancer Research Center (DKFZ)HeidelbergGermany
  15. 15.Department of Pediatric Oncology, Hematology and ImmunologyHeidelberg University HospitalHeidelbergGermany

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