Histopathology, November 2014, Vol.65(5), pp.613-622
To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/his.12431/abstract Byline: Christian Koelsche, Leonille Schweizer, Marcus Renner, Arne Warth, David T W Jones, Felix Sahm, David E Reuss, David Capper, Thomas Knosel, Birte Schulz, Iver Petersen, Alexis Ulrich, Eva Kristin Renker, Burkhard Lehner, Stefan M Pfister, Peter Schirmacher, Andreas Deimling, Gunhild Mechtersheimer Keywords: amplification; fusion; liposarcoma; NAB2; solitary fibrous tumour; STAT6 Aims 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. Methods and 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. Article Note: A.v.D. and G.M. contributed equally to this work. CAPTION(S): Figure S1. Copy number plots of five solitary fibrous tumours (SFTs) and nine dedifferentiated liposarcomas (DDLSs) derived from 450k array data with chromosomal gains (green) and chromosomal losses (red). Figure S2. Histological mimic of a solitary fibrous tumour (SFT) with absence of nuclear STAT6 expression (also depicted in Figure 1B). Figure S3. Solitary fibrous tumour (SFT) with strong nuclear STAT6 expression (A) and absence of MDM2 expression (B).
Amplification ; Fusion ; Liposarcoma ; 2 ; Solitary Fibrous Tumour ; 6