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

Shih Chiang Huang, Chien Feng Li, Yu-Chien Kao, I. Chieh Chuang, Hui Chun Tai, Jen Wei Tsai, Shih Chen Yu, Hsuan Ying Huang, Jui Lan, Shao Lun Yen, Po Chun Lin, Tse Ching Chen

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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.

Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalCancer Medicine
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Fingerprint

Solitary Fibrous Tumors
Gene Fusion
Mitosis
Histology
Angiofibroma
Staining and Labeling
Neoplasm Metastasis
Pleura
Giant Cells
Disease-Free Survival
Fats
Recurrence

Keywords

  • NAB2
  • Solitary fibrous tumor
  • STAT6
  • Thoracic
  • Translocation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors. / Huang, Shih Chiang; Li, Chien Feng; Kao, Yu-Chien; Chuang, I. Chieh; Tai, Hui Chun; Tsai, Jen Wei; Yu, Shih Chen; Huang, Hsuan Ying; Lan, Jui; Yen, Shao Lun; Lin, Po Chun; Chen, Tse Ching.

In: Cancer Medicine, Vol. 5, No. 2, 01.02.2016, p. 159-168.

Research output: Contribution to journalArticle

Huang, SC, Li, CF, Kao, Y-C, Chuang, IC, Tai, HC, Tsai, JW, Yu, SC, Huang, HY, Lan, J, Yen, SL, Lin, PC & Chen, TC 2016, 'The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors', Cancer Medicine, vol. 5, no. 2, pp. 159-168. https://doi.org/10.1002/cam4.572
Huang, Shih Chiang ; Li, Chien Feng ; Kao, Yu-Chien ; Chuang, I. Chieh ; Tai, Hui Chun ; Tsai, Jen Wei ; Yu, Shih Chen ; Huang, Hsuan Ying ; Lan, Jui ; Yen, Shao Lun ; Lin, Po Chun ; Chen, Tse Ching. / The clinicopathological significance of NAB2-STAT6 gene fusions in 52 cases of intrathoracic solitary fibrous tumors. In: Cancer Medicine. 2016 ; Vol. 5, No. 2. pp. 159-168.
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