Prognostic and diagnostic value of Ewing family of tumors (EFTs)-associated fusion transcripts detected in peripheral blood specimens.

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10538 Background: EFTs are characterized by chromosomal translocations leading to formation of oncogenic EWSR1-FLI1 fusion gene in 85-90% of cases. The aim of the study was to detect circulating tumor cells (CTCs) carrying EWSR1-FLI1 fusion transcript in peripheral blood and assess their added value to standard diagnostic procedures and utility as a prognostic marker in EFTs. Methods: 10mL of whole blood was collected from 35 untreated adult EFTs patients at the diagnosis (period: 2008-2011, median age 27 years) and 13 healthy controls. 13 patients presented metastatic disease (M1) at the diagnosis. Nested RT-PCR was applied in triplicate for the detection of EWSR1-FLI1 transcript. Blood specimen was regarded CTC-positive when at least 2 out of 3 nested RT-PCR assays were positive and results were confirmed by sequencing. FISH assay for EWSR1 rearrangement was performed on FFPE tumor tissue in 28 available cases. Median follow-up was 16 months. Results: EWSR1-FLI1 transcript was detected in peripheral blood of 71.4% (n=25) of patients. FISH assay was positive for EWRS1 rearrangement in 58% of cases. In 10 patients, where FISH assay could not be performed due to insufficient quality or lack of material, nested RT-PCR provided confirmation of immunopathological diagnosis. Specificity of RT-PCR blood test in healthy control was 91.4% (12/13 negative; p=0.0001). Median overall survival (OS) was 18 months. CTC-positive patients showed the trend for longer OS than CTC-negative patients (1-year OS: 89% vs. 58%; p=0.07), but longer follow-up is needed. Conclusions: Our results show that the fusion transcript detection in peripheral blood specimens may be a useful additional test to the standard clinicopathological diagnosis of EFTs. High detection rate of EWSR1-FLI1 transcript in peripheral blood of EFTs patients at the diagnosis may imply EFTs as a systemic disease with clinically evident metastases or micrometastases at presentation. Prognostic significance of CTCs in EFTs warrants further studies.