Interphase Fluorescent In Situ Hybridization Patterns in Translocation Associated Sarcomas
Danielle McClain, Hui Chen, Narasimhan Agaram, Suresh Jhanwar, Meera Hameed. Montefiore Medical Center, Bronx, NY; Memorial Sloan Kettering Cancer Center, New York, NY
Background: Interphase fluorescent in-situ hybridization (FISH) using break-apart probes is commonly used to diagnose chromosomal rearrangements in translocation associated sarcomas and is routinely performed on formalin fixed paraffin embedded tissue (FFPE). In this technique, the separation of the two probes indicate rearrangement of one of the genes without identification of the partner gene. It is a robust technique with clear signals of one fused signal of the probes representing the normal gene and two split signals representing the rearranged gene. This standard rearrangement pattern (SRG) can sometimes be accompanied by additional complex FISH patterns (CFP). These include duplications or amplification of normal gene and rearranged gene, loss or gain of 5' or 3' sequences and combinations of the above. In this study we retrospectively analyzed the FISH patterns in various translocation associated sarcomas.
Design: We collected pathological data and FISH results on the following translocation associated sarcomas for the last 5 years from the database of the Pathology Department at Memorial Sloan-Kettering Cancer Center. FISH results were available on twenty-five (25) Synovial Sarcomas (SS), eleven (11) Alveolar Rhabdomyosarcomas (ARMS), nine (9) desmoplastic small round cell tumors (DSRCT), four (4) Low grade fibromyxoid sarcomas (LGFMS), and three (3) myxoid liposarcomas (MLS).
Results: In this group complex FISH patterns (CFP) were encountered in SS, ARMS and myxoid liposarcomas. DSRCT and LGFMS showed only SRG of EWSR1 and FUS respectively. Eight out of twenty-five (32%) of Synovial sarcomas displayed complex FISH patterns, which included SRG and duplication or additional copies of native SYT/SS18 in 6 cases with or without loss of 5 ' or 3' sequences. ALL ARMS except for one case (90%) had complex FISH pattern. Duplication or multiple copies of SRG of the FKHR/FOXO1 gene was the most common complex pattern. Of the three MLS, two showed CFP which included duplication and loss of 5' in addition to SRG of the CHOP/DDIT3 gene. Both cases were high grade.
Conclusions: 1) Complex interphase FISH patterns are not uncommon in translocation associated sarcomas
2) In these small series, CFPs are highly prevalent in alveolar rhabdomyosarcoma
3) It is interesting that desmoplastic small round cell tumor, a highly aggressive neoplasm showed only standard rearrangement of the EWSR1 gene in all cases.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 31, Monday Afternoon