NAB2‐STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary fibrous tumors: the association between fusion variants and locations

Abstract

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm harboring NAB2-STAT6 fusion, which drives STAT6 nuclear relocation. For extrathoracic SFTs, the clinical relevance of this molecular hallmark remains obscure. We assessed STAT6 immunoexpression for 61 extrathoracic SFTs exclusive of the meninges and head and neck, and 25 had analyzable RNAs to distinguish fusion variants by RT-PCR. The immunohistochemical and molecular findings were correlated with clincopathological features and disease-free survival (DFS). Twenty-eight males and 33 females had SFTs in the body cavities (n = 31), extremities (n = 17), and trunk (n = 13), categorized into 53 non-malignant and 8 malignant tumors. The vast majority (n = 57, 93%) exhibited distinctive STAT6 nuclear expression, including malignant ones. The common fusion variants were NAB2ex6-STAT6ex16/17 in 13 SFTs and NAB2ex4-STAT6ex2 in 8, while miscellaneous variants were detected only in 4 SFTs in the limbs and trunk but not in any body cavity-based cases (P = 0.026). The worse DFS was univariately associated with malignant histology (P = 0.04) but unrelated to tumor size, location, or fusion variant. Conclusively, extrathoracic SFTs mostly harbor NAB2ex6-STAT6ex16/17, followed by NAB2ex4-STAT6ex2. Miscellaneous variants are significantly rare in SFTs within the body cavities. The clinical aggressiveness of extrathoraic SFTs is associated with malignant histology but unrelated to the NAB2-STAT6 fusion variants.

Solitary fibrous tumour of the genitourinary tract: a clinicopathological study of 11 cases and their association with theNAB2-STAT6fusion gene

“…Relationships were also examined between NAB2-STAT6 gene fusion variants, body site location, age and tumour size, and clinical outcomes of solitary fibrous tumours. Although the study did not demonstrate significant relationships, it highlights the potential use of fusion variants for outcome prediction 22. STAT6 immunohistochemistry probably suffices for diagnostic evaluation of solitary fibrous tumours.…”

“…An understanding of solitary fibrous tumours at this extrapleural site has become increasingly relevant with the discovery of the molecular hallmark NAB2-STAT6 gene fusion. Such genetic aberrations may improve diagnostic and prognostic accuracy and may foster elucidation of additional molecular mechanisms involved in tumorigenesis 2 13 16 22…”

“…In fact, investigators have suggested a prognostic relationship between different fusion variants and the behaviour of solitary fibrous tumours. For example, one study found that detected fusion variants related to particular anatomical subsites of extrathoracic solitary fibrous tumours 22. Relationships were also examined between NAB2-STAT6 gene fusion variants, body site location, age and tumour size, and clinical outcomes of solitary fibrous tumours.…”

Clinicopathological differences between variants of the NAB2–STAT6 fusion gene in solitary fibrous tumors of the meninges and extra-central nervous system

“…Because of the difference in terminology of SFT/HPC between meninges and other sites, it is difficult to compare the histology in all primary sites. While there were some reports that there was no statistical correlation between the histological variants and the NAB2-STAT6 fusion gene variants [25,26,28,31], Barthelmeb reported that there was a significant correlation between NAB2-STAT6 fusion gene and histological feature; fibrous SFT, cellular SFT and HPC in intrathoracic region, head and neck, and soft tissue and that most tumors with NAB2 exon 4-STAT6 exon 2/3 fusion are classical fibrous pleuropulmonary SFTs with a benign appearance, and most tumors with NAB2 exon 6-STAT6 exon 16/17 are cellular SFT and HPCs in the retroperitoneum and pelvis with cellular appearance, increased mitotic activity [12]. Based on Fritchie's study of meningeal SFTs, there was no significant difference between histology and NAB2-STAT6 fusion gene, while there was a significant difference between histology and tumor with/without NAB2 exon 4-STAT6 exon 3 fusion [32].…”

TERT promoter mutations in solitary fibrous tumour

“…The discovery of the NAB2–STAT6 fusion as the driving alteration in SFT suggested that specific chimeric fusion types may drive differential behaviour. But while different exonic fusion types show site and histological phenotype predilections, no correlation between NAB2–STAT6 fusion type and disease‐free survival has been reported to date …”