The clinicopathological significance of NAB2‐STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors

摘要

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. style="fixed-case">STAT6 distinctively decorated the tumoral nuclei in 51 (98%) style="fixed-case">SFTs. However, no nuclear staining was observed in the histological mimics. style="fixed-case">NAB2‐ style="fixed-case">STAT6 fusion was detected in 34 style="fixed-case">SFTs. Twenty‐nine (85.3%) exhibited the major style="fixed-case">NAB2ex4‐ style="fixed-case">STAT6ex2/3 variant and 5 (14.7%) the minor style="fixed-case">NAB2ex6‐ style="fixed-case">STAT6ex16/17. style="fixed-case">NAB2ex4‐ style="fixed-case">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 style="fixed-case">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 style="fixed-case">HPFs (P = 0.0012) but was unrelated to fusion variants. In conclusion, the majority of intrathoracic style="fixed-case">SFTs exhibited style="fixed-case">STAT6 nuclear staining, and style="fixed-case">NAB2ex4‐ style="fixed-case">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 style="fixed-case">NAB2‐ style="fixed-case">STAT6 fusion variants.