title: Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein.
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.
authors.affiliation: Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, INF 224, 69120, Heidelberg, Germany.
authors.forename: Leonille
authors.initials: L
authors.lastname: Schweizer
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.forename: Rosario M
authors.initials: RM
authors.lastname: Piro
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: David E
authors.initials: DE
authors.lastname: Reuss
authors.forename: Stefan
authors.initials: S
authors.lastname: Pusch
authors.forename: Antje
authors.initials: A
authors.lastname: Habel
authors.forename: Jochen
authors.initials: J
authors.lastname: Meyer
authors.forename: Tanja
authors.initials: T
authors.lastname: Göck
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.forename: Stephanie
authors.initials: S
authors.lastname: Heim
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Gunhild
authors.initials: G
authors.lastname: Mechtersheimer
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Rainer
authors.initials: R
authors.lastname: König
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D015331:Cohort Studies; D003937:Diagnosis, Differential; D059472:Exome; D006393:Hemangiopericytoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008577:Meningeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000502:physiology*; D054364:Solitary Fibrous Tumors / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: C491000:NAB2 protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human