title: Differential diagnosis of solitary fibrous tumors: A study of 454 soft tissue tumors indicating the diagnostic value of nuclear STAT6 relocation and ALDH1 expression combined with in situ proximity ligation assay.
abstract: Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms, displaying variable morphological and clinicopathological features. Supportive immunohistochemical markers such as CD34, CD99, BCL2 and LSD1 are commonly applied in the differential diagnosis of SFTs, although none is sufficiently sensitive or specific enough. The aim of the present study was to examine the most differential markers for the reliable distinction of SFTs from histological mimics. We investigated the expression of STAT6, NAB2, ALDH1, GRIA2 and IGF2 in 454 comprehensive soft tissue tumors, comprising formalin-fixed paraffin-embedded (FFPE) tissue samples from 80 SFTs and 374 other mesenchymal tumors. The Duolink in situ proximity ligation assay (PLA) was adopted for the detection of NAB2-STAT6 fusion proteins. STAT6 was expressed in all 80 SFT cases with a moderate-strong nuclear staining intensity. In contrast, only 4/374 (1%) non-SFT mesenchymal tumors showed a nuclear STAT6 staining pattern. Strong expression of NAB2 and IGF2 was detected in SFT and non-SFT cases. Positive GRIA2 immunoreactivity was found in 64% (SFT) and 8% (non-SFT), respectively. Expression of ALDH1 was moderate-strong in 76% (SFT), whereas only 2 non-SFT lesions showed positive ALDH1 immunoreactivity. Moreover, the presence of NAB2‑STAT6 fusion proteins was indicated in 71/78 (91%) SFT cases by PLA. Nuclear STAT6 and cytoplasmic ALDH1 expression are the most sensitive and specific markers in the differential diagnosis of SFTs. Furthermore, application of Duolink in situ proximity ligation assay can be helpful to detect the NAB2-STAT6 fusion protein in the majority of SFTs.
authors.affiliation: Department of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Shaida
authors.initials: S
authors.lastname: Ouladan
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Trautmann
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Orouji
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartmann
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Huss
authors.affiliation: Department of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D054364:Solitary Fibrous Tumors / Q000175:diagnosis* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; C491000:NAB2 protein, human; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase