Open AccessThe clinicopathological significance of NAB 2‐ STAT 6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors
Author(s) -
Huang ShihChiang,
Li ChienFeng,
Kao YuChien,
Chuang IChieh,
Tai HuiChun,
Tsai JenWei,
Yu ShihChen,
Huang HsuanYing,
Lan Jui,
Yen ShaoLun,
Lin PoChun,
Chen TseChing
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.572
Subject(s) - pathology , solitary fibrous tumor , stat , medicine , histology , immunohistochemistry , histopathology , cd34 , biology , gene , stat3 , biochemistry , genetics , stem cell
NAB 2‐ STAT 6 gene fusion drives STAT 6 nuclear expression and is the pathognomonic hallmark of solitary fibrous tumors ( SFT s). However, no study has systematically analyzed the clinicopathological features, STAT 6 immunoexpression status, or the fusion variants of NAB 2‐ STAT 6 in intrathoracic SFT s. Fifty‐two intrathoracic SFT s were retrieved to appraise histopathology, assess STAT 6 immunoexpression, and determine NAB 2‐ STAT 6 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 SFT s, including two fat‐forming and two giant cell angiofibroma‐like SFT s. STAT 6 distinctively decorated the tumoral nuclei in 51 (98%) SFT s. However, no nuclear staining was observed in the histological mimics. NAB 2‐ STAT 6 fusion was detected in 34 SFT s. Twenty‐nine (85.3%) exhibited the major NAB 2ex4‐ STAT 6ex2/3 variant and 5 (14.7%) the minor NAB 2ex6‐ STAT 6ex16/17 . NAB 2ex4‐ STAT 6ex2 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 SFT s, 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 HPF s ( P = 0.0012) but was unrelated to fusion variants. In conclusion, the majority of intrathoracic SFT s exhibited STAT 6 nuclear staining, and NAB 2ex4‐ STAT 6ex2/3 was the predominant fusion type. However, clinical aggressiveness is associated with atypical/malignant histology primarily contributed by increased mitosis but was unrelated to the NAB 2‐ STAT 6 fusion variants.