OVERVIEW
Ewing Sarcoma (a.k.a. primitive neuroectodermal tumours or PNET) cases account for less than 10% of primary malignant bone tumours; however, it is the most common sarcoma of bone in children and young adults with a peak incidence in the second decade of life. The most common sites of involvement are in the diaphysis or metaphyseal-diaphyseal portion of the long bones, pelvis, or ribs.
Up to 85% of Ewing sarcoma harbour a t(11;22)(q24;q12) that results in the fusion of the 5’ portion of EWSR1 on chromosome 22 to the 3’ portion of FLI1 on chromosome 11. There are several other ETS transcription factors that fuse to EWSR1 with 5-15% of cases having an EWRS1/ERG (t(21;22)(q22;q12)) fusion and another 1-5% of sarcomas harbouring fusions of EWSR1 with ETV1, FEV and ETV4. In addition, there are reports of other non-ETS family fusion partners with EWSR1. There are also rare reports of EWSR1 being replaced with FUS which is part of the same family as EWSR1. There does not seem to be conclusive data showing a difference in prognosis between the different EWRS1 fusion partners.
TEST REQUIREMENTS
- Completed CGL Cytogenetics Solid Tumour Testing requisition form
- FFPE Tumour specimen (see Specimen Guidelines, Cytogenetics FISH FFPE test type)
- An H&E stained slide with the tumour region circled, and the estimated % tumour content written in the Tumour Content field of the requisition. NOTE: A minimum of 10% tumour and at least 200 nuclei is required.
- Specimen block and/or at least one unstained slide for each probe requested.
- See our FFPE Guidelines for additional details.
TURN-AROUND TIME
Results are reported within fourteen days from receipt of specimen and completed requisition form.
RESULTS REPORTING
- Specimens are reported as Positive for a rearrangement, Negative for a rearrangement.
- Greater than 95% of Ewing sarcomas will have an EWSR1 rearrangement
METHOD
FISH analysis is performed on the provided paraffin embedded tissue using the EWSR1 (22q12) dual colour, break-apart probe (Vysis) and an “in house” dual colour, break-apart probe (RP11-1079A6 and RP11-75P14) to FLI1 (11q24.3).
EWSR1 negative tumours with a high suspicion of Ewing sarcoma can be probed with the FUS (16p11) dual-colour, break-apart probe (Vysis).
REFERENCES
- Bridge et al Mod Pathol (2006) PMID: 16258512.
- Le Deley et al J Clin Oncol (2010) PMID: 20308673