[83] Genetic Testing in the Evaluation of Low-Grade Fibromyxoid Sarcoma.

Michael D Weindel, Wei-Lien Wang, Elizabeth Demicco, Harry L Evans, Vivian S Hernandez, Trang T Ton, 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

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a mesenchymal neoplasm with relatively bland histology, nonetheless 5-10% of cases metastasize. A balanced translocation, t(7;16)(q32-q34;p11), fusing the 5' portion of FUS to the 3' portion of CREB3L2 or in a minority of tumors CREB3L1 on chromosome 11p11 is characteristic. A subset of cases harbor a supernumerary ring chromosome with gain of material from chromosomes 7 and 16, possibly associated with a more aggressive clinical behavior. We examined 26 cases of LGFMS for the presence of a FUS rearrangement by FISH, and for FUS/CREB3L2, FUS/CREB3L1 fusion transcripts by RT-PCR. Additionally, FUS copy number was examined by FISH. The findings were correlated with the clinical and pathological features.
Design: Available FFPE tissue from 26 LGFMS cases from 1994-2010 were retrieved from the pathology files of our institutions and tabulated with clinical information. FISH analysis using unstained slides was performed using a commercially available FUS break-apart probe on all cases. FUS/CREB3L2 and FUS/CREB3L1 RT-PCR was performed as previously described (Guillou et al.) using tissue blocks (12 cases) and unstained slides (13 cases). Amplicons from all positive cases were sequenced by the Sanger method.
Results: The age of presentation ranged from 4 to 85 years (median, 37) with a slight male predominance. The location varied from extremities to trunk; 3 cases metastasized. FISH detected a FUS rearrangement in 20/22 informative cases. Of these, 3 cases showed an extra rearranged copy of FUS. None of these 3 cases metastasized; however 2 cases were locally aggressive. Of the 25 cases evaluated by RT-PCR, 18 cases were excluded due to poor RNA quality, and 6 of 7 informative cases were positive for FUS/CREB3L2 with sequence confirmation. RT-PCR and FISH showed complete correlation (n= 5).
Conclusions: A FUS gene rearrangement was found in most cases. Locally aggressive tumor behavior was noted in 2/3 cases carrying an extra copy of FUS, raising the possibility of an association with a more aggressive clinical phenotype. In addition to being useful to evaluate FUS copy number, FISH was found to be more often informative to detect FUS re-arrangements than RT-PCR, when testing archival FFPE tumor samples.
Category: Bone & Soft Tissue

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 16, Tuesday Morning


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