Complex Interphase Fluorescent In Situ Hybridization Patterns of EWSR1 Gene in Ewing Sarcoma Using Break Apart Probes
Hui Chen, Danielle McClain, Suresh C Jhanwar, Narasimhan P Agaram, Meera R Hameed. Memorial Sloan Kettering Cancer Center, New York, NY
Background: Chromosomal translocations are seen in about one-fourth of all sarcomas. Interphase fluorescent in-situ hybridization (FISH) using break-apart probes has provided the means for widespread use of this technique for sarcoma diagnosis in formalin fixed paraffin embedded tissue. While a typical positive result of a break-apart probe shows one fused signal for normal gene and a split signal indicating the rearranged gene, it is not uncommon to encounter complex FISH patterns (CFP). These include duplications or amplification of native 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 Ewing Sarcoma.
Design: We collected pathological data and FISH results on Ewing sarcoma cases where FISH was performed for the last 5 years from database of Pathology Department at Memorial Sloan-Kettering Cancer Center. Thirty-six patients were identified. There were 26 males and 10 females. Twenty three cases were primary bone, 10 cases were soft tissue (including 1 kidney, 1 prostate, 1 abdominal cavity) and 3 cases were primary chest wall.
Results: In this group, complex FISH patterns were encountered in eleven out of thirty-six (30%) cases. Majority (8) showed duplication of native EWSR1 in addition to standard rearrangement (SRG) and/or in association with duplication or loss of 5' or 3' sequences. Of the 11 cases with CFP the male:female ratio was 1.75:1 as compared to 3.2:1 in cases with SRG. The mean age in both groups (CFP and SRG) were 26.4 years and 26.8 years respectively. Metastases at time of presentation was seen in 56% (6/11) in the CFP group and 36% (9/25) in the SRG group. Fourteen out of nineteen patients (74%) were alive at 18 month follow-up in the SRG group whereas two out five patients (40%) are alive at 18 month follow-up in the CFP group.
Conclusions: 1) In addition to standard rearrangement, up to one-third of Ewing Sarcoma patients harbor complex FISH patterns.
2) There is a trend towards high stage presentation in patients with complex FISH patterns.
3) Additional studies with larger number of patients and longer follow-up will aid in understanding the biological significance of these complex FISH patterns.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 1, Monday Afternoon