Molecular Characterization of a Series of Solitary Fibrous Tumors, including Immunohistochemical expression of STAT6 and NATB2-STAT6 Fusion Transcripts, using Reverse Transcriptase(RT)–Polymerase Chain Reaction(PCR) Technique: An Indian Experience

Publication date: Available online 26 August 2017
Source:Pathology - Research and Practice
Author(s): Bharat Rekhi, Omshree Shetty, Parul Tripathi, Prachi Bapat, Mukta Ramadwar, Jyoti Bajpai, Ajay Puri
A solitary fibrous tumor (SFT) is characterized by a diverse clinicopathologic spectrum. Recent studies have unraveled STAT6 as a useful diagnostic immunohistochemical (IHC) marker for a SFT and NAB2-STAT6 as its specific gene fusion transcript.Thirty-three SFTs were tested for STAT6 immunostaining by polymer detection technique. STAT6 immunoexpression was further graded, based on intensity (mild, moderate and strong) and percentage of immunopositive tumor cells, ranging from 1–25%(1+); 26–50%(2+); 51–75%(3+) and in more than 75%(4+) tumor nuclei.These cases along with 17 other tumors were tested for 8 variants of NAB2-STAT6, using qualitative endpoint reverse-transcriptase (RT)-PCR technique. RNA extraction was performed using Recover All Total nucleic acid extraction kit. The selected cases were screened for all the 8 fusion variants, using 8 primer pairs for NAB2 and STAT6 genes.Thirty-three SFTs occurred in 18 men and 15 women (M: F=1.2:1), with age varying from 13–74 years(average=49.6); across various body sites. Immunohistochemically, most SFTs (30/33) (90.9%) displayed moderate to strong immunostaining for STAT6, including 3+ and 4+ immunostaining patterns in 27/33 (81.8%) tumors. By RT-PCR, 30/33(90.9%) cases of SFT were positive for NAB2-STAT6 fusions, including NAB2ex4/STAT6ex2 (7cases), NAB2ex7/STAT6ex2 (7cases), NAB2ex6/STAT6ex3 (6cases), NAB2ex6/SAT6ex16 (4cases), NAB2ex3/STAT6ex19 (4cases), NAB2ex6/STAT6ex17 (single case), NAB2ex4/STAT6ex4 (single case) and NAB2ex6/STAT6ex18 (none). NAB2-STAT6 fusions were not observed in 9 cases of synovial sarcoma, 4 of Ewing sarcoma, 2 of MPNST and 2 cases of dedifferentiated liposarcomas (100% specificity). On comparing with clinical outcomes, more cases (7/11)(63.6%) of classic SFT were associated with favorable outcomes, while more cases(5/8)(62%) of atypical and malignant SFTs were associated with aggressive outcomes.This study reinforces high sensitivity and specificity of NAB2-STAT6 fusion and its correlation with strong and diffuse IHC expression of STAT6 in a SFT, irrespective of its occurrence in various body sites and its histopathologic types. NAB2ex4-STAT6ex2 and NAB2ex7-STAT6ex2 fusions were relatively more frequently observed in our patients. Atypical and malignant SFTs, together, were more frequently associated with relatively aggressive clinical outcomes.



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