title: Diagnostic utility of NCOA2 fluorescence in situ hybridization and Stat6 immunohistochemistry staining for soft tissue angiofibroma and morphologically similar fibrovascular tumors.
abstract: Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor cells with abundant collagenous to myxoid stroma and branching small vessels. The lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal translocation of t(5;8)(p15;q13). However, morphologically similar tumors containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We designed an original DNA probe for detecting NCOA2 split signals on fluorescence in situ hybridization (FISH) and estimated its utility with 20 fibrovascular tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor, retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found moderate to strong nuclear Stat6 expression in all SFTs but no expression in the other tumors. Both estrogen receptor and progesterone receptor expressions were observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma protein was found in less than 10% of cells in all tumor types except myxoid liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4. All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved effective for the differential diagnosis of STA, even when using small biopsy specimens.
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sugita
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Aoyama
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Keira
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Ogino
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kaya
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emori
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Orthopedic Surgery, St Marianna University School of Medicine, Kawasaki 216-8511, Japan.
authors.forename: Hisaya
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Diagnostic Pathology, St Marianna University School of Medicine, Kawasaki 216-8511, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. Electronic address: hasetada@sapmed.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018322:Angiofibroma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D003937:Diagnosis, Differential; D005260:Female; D005354:Fibrosarcoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018208:Liposarcoma, Myxoid / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D050800:STAT6 Transcription Factor
keywords: Fluorescence in situ hybridization; Immunohistochemistry; NCOA2 split signal; Soft tissue angiofibroma; Stat6