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

Abstract

Investigations on the NAB2-STAT6 fusion gene in solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have increased since its discovery in 2013. Although several SFTs reported without NAB2-STAT6 fusion gene analysis, we reviewed 546 SFTs/HPCs with NAB2-STAT6 fusion gene analysis in this study and investigated differences between the gene variants. In total, 452 cases tested positive for the NAB2-STAT6 fusion gene, with more than 40 variants being detected. The most frequent of these were NAB2 exon 6-STAT6 exon 16/17/18 and NAB2 exon 4-STAT6 exon 2/3, with the former occurring most frequently in SFTs in meninges, soft tissues, and head and neck; the latter predominated in SFTs in the pleura and lung. There was no difference between the histology of SFTs and fusion gene variants. A follow-up analysis of SFTs showed that 51 of 202 cases had a recurrence, with 18 of 53 meningeal SFTs having a local recurrence and/or metastasis within 0-19 years. In meninges and soft tissue, SFTs with the NAB2 exon 6-STAT6 exon 16/17/18 tended to recur more frequently than SFTs with the NAB2 exon 4-STAT6 exon 2/3. Clinicopathological data, including yearly follow-ups, are required for meningeal SFTs/HPCs to define the correlation of variants of NAB2-STAT6 fusion gene.

Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients

“…Further advances in grading SFT/HPC might be possible by integrating molecular information into specific grading subgroups. For example, different NAB2‐STAT6 gene fusion variants in soft tissue SFTs are reportedly correlated to different clinical outcomes, and TERT promoter mutations have also been associated with adverse prognosis . The prognostic relevance of these molecular aberrations in CNS SFTs/HPCs needs to be further investigated in a larger number of tumors .…”

Primary paediatric epidural sarcomas: molecular exploration of three cases

“…Furthermore, it has been reported that sarcoma patients whose tumours were interrogated by NGS as part of their clinical management received the option of access to targeted agents in their treatment [31]. This is because a difference in clinical outcome may be predicted by one or more of the following: firstly, incidence of a specific fusion; next, the presence of one or more variants of a fusion; or finally, the presence of one of a heterogeneous group of unrelated fusions [32, 33]. More significantly, as the cases in discussion are rare paediatric tumours, an isolated fusion found in a single patient can be important, especially for future therapeutic targeting [3].…”

Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression

“…20 Even if they are associated with grading, the types of fusion variants are not associated with prognosis, recurrence-free survival, or overall survival. 2,12,20 Malignant progression may be just one of several mechanisms provoking recurrence and metastasis. There is a strong tendency for Grade III tumors to produce more metastases and a shorter overall survival and recurrencefree interval in some studies (for example, overall survival of 256 months vs 114 months and recurrence-free interval of 95 months vs 59 months for Grade III vs lower-grade tumors, respectively 10 ).…”