Clinical Utility of MYH9/USP6 Fusion Transcript Detection and USP6 Expression in Nodular Fasciitis
Nimesh R Patel, Elizabeth G Demicco, Angela M Major, Wei-Lien Wang, Alexander J Lazar, Dolores Lopez-Terrada. Baylor College of Medicine/Texas Children's Hospital, Houston, TX; The University of Texas M.D. Anderson Cancer Center, Houston, TX
Background: Nodular fasciitis (NF) is a self-limited myofibroblastic lesion which can be misdiagnosed as a sarcoma as a result of its rapid growth, prominent mitotic activity, and cellularity. Recently, a recurrent translocation t(17;22) has been identified, resulting in the fusion of USP6 to the promoter region of MYH9, and driving increased USP6 expression. We developed a novel RT-PCR assay to detect MYH9/USP6 fusion transcripts in formalin fixed paraffin embedded (FFPE) and frozen tissue, and examined USP6 protein overexpression by immunohistochemical (IHC) study.
Design: 11 cases of NF with available clinical information were retrieved from the pathology files of our institutions from 2004-2011. Ages of presentation ranged from 12 to 65 years with a male: female ratio of 2.7:1. Locations included the upper extremity, face, and pelvis. Novel PCR primers were designed to optimize an RT-PCR assay for the detection of the two previously described splice variants using frozen and FFPE specimens. Representative FFPE tissue from 11 NF cases and 1 case of cranial fasciitis, and frozen tissue from 1 NF case, were tested by RT-PCR. Amplicons from all positive cases were characterized by sequencing. Corresponding immunohistochemical analysis for USP6 expression (polyclonal, 1:20, Sigma-Aldrich) was also performed in all cases.
Results: 9 of 11 (81%) NF cases were positive for MYH9/USP6 fusion transcripts by RT-PCR while the cranial fasciitis specimen was negative. All of the positive cases showed increased expression of USP6 by IHC.
Conclusions: RT-PCR for MYH9/USP6 fusion transcript detection is diagnostically useful for NF surgical specimens and core needle biopsies. In our study, the presence of the fusion transcript correlated with increased expression of USP6, as detected by IHC. RT-PCR and IHC testing of additional cases is ongoing, and the results are being validated using a USP6 break-apart FISH assay currently under development.
Category: Bone & Soft Tissue
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 11, Monday Morning