NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors

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

Research output: Contribution to journalArticle

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Abstract

Solitary fibrous tumor (SFT) is characterized by the inv12(q13q13)-derived NAB2-STAT6 fusion, which exhibits variable breakpoints and drives STAT6 nuclear expression. The implications of NAB2-STAT6 fusion variants in pathological features and clinical behavior remain to be characterized in a large cohort of SFTs. We investigated the clinicopathological correlates of this genetic hallmark and analyzed STAT6 immunoexpression in 28 intrathoracic, 37 extrathoracic, and 23 meningeal SFTs. These 88 tumors were designated as histologically nonmalignant in 75 cases and malignant in 13, including 1 dedifferentiated SFT. Eighty cases had formalin-fixed and/or fresh samples to extract assessable RNAs for RT-PCR assay, which revealed NAB2-STAT6 fusion variants comprising 12 types of junction breakpoints in 73 fusion-positive cases, with 65 (89%) falling into 3 major types. The predominant NAB2ex4-STAT6ex2 (n=33) showed constant breakpoints at the ends of involved exons, whereas the NAB2ex6-STAT6ex16 (n=16) and NAB2ex6-STAT6ex17 (n=16) might exhibit variable breakpoints and incorporate NAB2 or STAT6 intronic sequence. Including 73 fusion-positive and 7 CD34-negative SFTs, STAT6 distinctively labeled 87 (99%) SFTs in nuclei, exhibited diffuse reactivity in 73, but did not decorate 98 mimics tested. In seven fusion-negative cases, 6 were STAT6-positive, suggesting rare fusion variants not covered by RT-PCR assay. Regardless of histological subtypes, intrathoracic SFTs affected older patients (P=0.035) and tended to be larger in size (P=0.073). Compared with other variants, NAB2ex4-STAT6ex2/4 fusions were significantly predominant in the SFTs characterised by intrathoracic location (P<0.001), older age (P=0.005), decreased mitoses (P=0.0028), and multifocal or diffuse STAT6 staining (P=0.013), but not found to correlate with disease-free survival. Conclusively, STAT6 nuclear expression was distinctive in the vast majority of SFTs, including all fusion-positive tumors, and exploitable as a robust diagnostics of CD34-negative cases. Despite the associations of NAB2-STAT6 fusion variants with several clincopathological factors, their prognostic relevance should be further validated in large-scale prospective studies of SFTs.

Original languageEnglish
Pages (from-to)1324-1335
Number of pages12
JournalModern Pathology
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 3 2015

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Solitary Fibrous Tumors
Polymerase Chain Reaction
Mitosis
Formaldehyde
Disease-Free Survival
Exons
Neoplasms
Prospective Studies
RNA
Staining and Labeling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Tai, H. C., Chuang, I. C., Chen, T. C., Li, C. F., Huang, S. C., Kao, Y-C., ... Huang, H. Y. (2015). NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors. Modern Pathology, 28(10), 1324-1335. https://doi.org/10.1038/modpathol.2015.90

NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors. / Tai, Hui Chun; Chuang, I. Chieh; Chen, Tse Ching; Li, Chien Feng; Huang, Shih Chiang; Kao, Yu-Chien; Lin, Po Chun; Tsai, Jen Wei; Lan, Jui; Yu, Shih Chen; Yen, Shao Lun; Jung, Shih Ming; Liao, Kuan Cho; Fang, Fu Min; Huang, Hsuan Ying.

In: Modern Pathology, Vol. 28, No. 10, 03.10.2015, p. 1324-1335.

Research output: Contribution to journalArticle

Tai, HC, Chuang, IC, Chen, TC, Li, CF, Huang, SC, Kao, Y-C, Lin, PC, Tsai, JW, Lan, J, Yu, SC, Yen, SL, Jung, SM, Liao, KC, Fang, FM & Huang, HY 2015, 'NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors', Modern Pathology, vol. 28, no. 10, pp. 1324-1335. https://doi.org/10.1038/modpathol.2015.90
Tai, Hui Chun ; Chuang, I. Chieh ; Chen, Tse Ching ; Li, Chien Feng ; Huang, Shih Chiang ; Kao, Yu-Chien ; Lin, Po Chun ; Tsai, Jen Wei ; Lan, Jui ; Yu, Shih Chen ; Yen, Shao Lun ; Jung, Shih Ming ; Liao, Kuan Cho ; Fang, Fu Min ; Huang, Hsuan Ying. / NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors. In: Modern Pathology. 2015 ; Vol. 28, No. 10. pp. 1324-1335.
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AU - Yen, Shao Lun

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AU - Fang, Fu Min

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N2 - Solitary fibrous tumor (SFT) is characterized by the inv12(q13q13)-derived NAB2-STAT6 fusion, which exhibits variable breakpoints and drives STAT6 nuclear expression. The implications of NAB2-STAT6 fusion variants in pathological features and clinical behavior remain to be characterized in a large cohort of SFTs. We investigated the clinicopathological correlates of this genetic hallmark and analyzed STAT6 immunoexpression in 28 intrathoracic, 37 extrathoracic, and 23 meningeal SFTs. These 88 tumors were designated as histologically nonmalignant in 75 cases and malignant in 13, including 1 dedifferentiated SFT. Eighty cases had formalin-fixed and/or fresh samples to extract assessable RNAs for RT-PCR assay, which revealed NAB2-STAT6 fusion variants comprising 12 types of junction breakpoints in 73 fusion-positive cases, with 65 (89%) falling into 3 major types. The predominant NAB2ex4-STAT6ex2 (n=33) showed constant breakpoints at the ends of involved exons, whereas the NAB2ex6-STAT6ex16 (n=16) and NAB2ex6-STAT6ex17 (n=16) might exhibit variable breakpoints and incorporate NAB2 or STAT6 intronic sequence. Including 73 fusion-positive and 7 CD34-negative SFTs, STAT6 distinctively labeled 87 (99%) SFTs in nuclei, exhibited diffuse reactivity in 73, but did not decorate 98 mimics tested. In seven fusion-negative cases, 6 were STAT6-positive, suggesting rare fusion variants not covered by RT-PCR assay. Regardless of histological subtypes, intrathoracic SFTs affected older patients (P=0.035) and tended to be larger in size (P=0.073). Compared with other variants, NAB2ex4-STAT6ex2/4 fusions were significantly predominant in the SFTs characterised by intrathoracic location (P<0.001), older age (P=0.005), decreased mitoses (P=0.0028), and multifocal or diffuse STAT6 staining (P=0.013), but not found to correlate with disease-free survival. Conclusively, STAT6 nuclear expression was distinctive in the vast majority of SFTs, including all fusion-positive tumors, and exploitable as a robust diagnostics of CD34-negative cases. Despite the associations of NAB2-STAT6 fusion variants with several clincopathological factors, their prognostic relevance should be further validated in large-scale prospective studies of SFTs.

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