Nuclear relocation of STAT6 reliably predicts NAB2-STAT6 fusion for the diagnosis of solitary fibrous tumour.
OBJECTIVE
Nuclear relocation of STAT6 has been shown in tumours with NAB2-STAT6 fusion, and has been proposed as an ancillary marker for the diagnosis of solitary fibrous tumours (SFTs). The aim of this study was to verify the utility of STAT6 immunohistology in diagnosing SFT.


RESULTS
A total of 689 formalin-fixed paraffin-embedded tumours comprising 35 pleural SFTs and 654 other mesenchymal tumours were investigated for STAT6 expression using immunohistochemistry. Nine dedifferentiated liposarcomas (DDLSs) and five SFTs were also examined for the presence of NAB2-STAT6 fusion at the protein level using the proximity ligation assay (PLA), and for copy number variants (CNVs) with the Illumina Infinium Human Methylation450 array. Thirty-four of 35 SFTs showed strong nuclear STAT6 expression. Furthermore, five of 68 DDLSs, two of 130 undifferentiated pleomorphic sarcomas and one of 63 cases of nodular fasciitis showed moderate to strong nuclear STAT6 expression. The PLA indicated the presence of NAB2-STAT6 fusion protein in SFTs, but signal was also detected in some DDLSs. Copy number analysis showed an overall low frequency of chromosomal imbalances in SFTs, but complex karyotypes in DDLSs, including amplification of STAT6 and MDM2 loci.


CONCLUSIONS
The detection of nuclear relocation of STAT6 with immunohistochemistry is a characteristic of SFTs, and may serve as a diagnostic marker that indicates NAB2-STAT6 fusion and helps to discriminate SFTs from histological mimics.
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; German Cancer Consortium (DKTK), CCU Neuropathology German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Christian
C
Koelsche
Leonille
L
Schweizer
Marcus
M
Renner
Arne
A
Warth
David T W
DT
Jones
Felix
F
Sahm
David E
DE
Reuss
David
D
Capper
Thomas
T
Knösel
Birte
B
Schulz
Iver
I
Petersen
Alexis
A
Ulrich
Eva Kristin
EK
Renker
Burkhard
B
Lehner
Stefan M
SM
Pfister
Peter
P
Schirmacher
Andreas
A
von Deimling
Gunhild
G
Mechtersheimer
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D056915:DNA Copy Number Variations; D050939:Gene Fusion; D006801:Humans; D007150:Immunohistochemistry; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016612:Paraffin Embedding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D054364:Solitary Fibrous Tumors / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; C491000:NAB2 protein, human; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human
NAB2; STAT6; amplification; fusion; liposarcoma; solitary fibrous tumour