title: The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors.
abstract: NAB2-STAT6 gene fusion drives STAT6 nuclear expression and is the pathognomonic hallmark of solitary fibrous tumors (SFTs). However, no study has systematically analyzed the clinicopathological features, STAT6 immunoexpression status, or the fusion variants of NAB2-STAT6 in intrathoracic SFTs. Fifty-two intrathoracic SFTs were retrieved to appraise histopathology, assess STAT6 immunoexpression, and determine NAB2-STAT6 fusion variants by RT-PCR. Location-relevant histologic mimics served as controls. Thirty-one pleura-based, 12 mediastinal/pericardial, and nine intrapulmonary lesions were histologically categorized into eight malignant, eight atypical, and 36 conventional or cellular SFTs, including two fat-forming and two giant cell angiofibroma-like SFTs. STAT6 distinctively decorated the tumoral nuclei in 51 (98%) SFTs. However, no nuclear staining was observed in the histological mimics. NAB2-STAT6 fusion was detected in 34 SFTs. Twenty-nine (85.3%) exhibited the major NAB2ex4-STAT6ex2/3 variant and 5 (14.7%) the minor NAB2ex6-STAT6ex16/17. NAB2ex4-STAT6ex2 was significantly associated with older age (P = 0.01) and pleuropulmonary tumors (P = 0.025). After a median follow-up of 33.9 (range, 0.3-174.6) months, adverse outcomes occurred in one atypical and five malignant SFTs, including two local relapses, one intrapulmonary metastasis, and three extrathoracic metastases. Inferior disease-free survival was univariately associated with atypical/malignant histology (P = 0.001) and a mitosis >4/10 HPFs (P = 0.0012) but was unrelated to fusion variants. In conclusion, the majority of intrathoracic SFTs exhibited STAT6 nuclear staining, and NAB2ex4-STAT6ex2/3 was the predominant fusion type. However, clinical aggressiveness is associated with atypical/malignant histology primarily contributed by increased mitosis but was unrelated to the NAB2-STAT6 fusion variants.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Shih-Chiang
authors.identifier: http://orcid.org/0000-0002-5092-4434
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chien
authors.initials: YC
authors.lastname: Kao
authors.affiliation: Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: I-Chieh
authors.initials: IC
authors.lastname: Chuang
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Tai
authors.affiliation: Department of Anatomic Pathology, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Jen-Wei
authors.initials: JW
authors.lastname: Tsai
authors.affiliation: Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shih-Chen
authors.initials: SC
authors.lastname: Yu
authors.affiliation: Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.affiliation: Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jui
authors.initials: J
authors.lastname: Lan
authors.affiliation: Departments of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shao-Lun
authors.initials: SL
authors.lastname: Yen
authors.affiliation: Departments of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D050800:STAT6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D054364:Solitary Fibrous Tumors / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D013899:Thoracic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; C491000:NAB2 protein, human; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor
keywords: NAB2; STAT6; solitary fibrous tumor; thoracic; translocation