Ewing Sarcoma Family of Tumors

Abstract

The Ewing sarcoma family of tumors (ESFT) comprises morphologically heterogeneous tumors that are characterized by nonrandom chromosomal translocations involving the EWS gene and one of several members of the ETS family of transcription factors. The translocation t(11;22)(q24;q12) is the most common and leads to the formation of the EWS-FLI1 fusion protein, which contributes to ESFT pathogenesis by modulating the expression of target genes. Tumors may be composed of small uniform cells with minimal morphologic evidence of differentiation, or they may be composed of larger, less uniform cells with varying degrees of neuroectodermal differentiation. CD99 expression is identified in nearly all ESFT and constitutes a useful positive marker when used as part of a panel of immunostains that can help rule out other differential diagnostic considerations. Molecular diagnostic tests commonly used to detect the presence of ESFT-specific translocations include RT-PCR and fluorescence in situ hybridization. Current therapy for patients with ESFT includes chemotherapy and surgery with or without radiation therapy. At present, the most significant prognostic factor for patients with ESFT is whether the disease is localized or metastatic.

An Unusual Cause of Lumbar Radiculopathy

“…Extraspinal causes of radiculopathy have been described in large retrospective reviews [10,11]. Pelvic causes of radicular pain may arise from extrinsic compression of the lumbosacral plexus as it traverses the true pelvis or as the L3-S4 nerve roots coalesce to form the sciatic nerve before exit through the greater sciatic foramen.…”

Inducible Expression of Chimeric EWS/ETS Proteins Confers Ewing's Family Tumor-Like Phenotypes to Human Mesenchymal Progenitor Cells

“…Since EFT has a poor prognosis, it is important to elucidate the underlying pathogenic mechanisms for establishing a more effective therapeutic strategy. EFT is characterized by the presence of chimeric genes composed of EWS and ets transcription factor genes (ETS) formed by specific chromosomal translocations, i.e., EWS/FLI1, t(11;22)(q24;q12); EWS/ERG, t(21;22)(q12;q12); EWS/ETV1, t(7;22)(p22;q12); EWS/E1AF, t(17;22)(q12;q12); and EWS/FEV, t(2;22)(q33;q12) (26). The products of these chimeric genes behave as aberrant transcriptional regulators and are believed to play a crucial role in the onset and progression of EFT (3,36).…”

Establishment and Characterization of a Clonal Human Extraskeletal Ewing's Sarcoma Cell Line, EES1

“…The ESFT comprises morphologically heterogeneous tumors that are characterized by nonrandom chromosomal translocations involving the EWS gene and one of several members of the ESFT of transcription factors (Khoury 2005). The expression of EWS/FLI-1 or EWS/ERG chimeric genes was found to be generated through a t(11;22)(q24;q12) or a t(21;22)(q22;q12) translocation (Urano et al 1996).…”

“…Molecular techniques used to identify this translocation along with the knowledge that the protein product of the MIC2 gene is highly expressed on the cell surface have greatly improved diagnostic abilities in the ESFT (Grier 1997). The translocation t(11;22)(q24;q12) is the most common feature (about 90%) and results in the formation of the EWS-FLI-1 fusion protein (Khoury 2005). About 10% of cases with ESFT express EWS-ERG (Kaneko et al 1997).…”

“…Both Ewing's sarcoma/PNET cells express the MIC2 gene in high amounts, which represents a highly selective and almost unique feature of these cells, making an assignment of these tumors in one entity even more likely (Ambros et al 1991). Khoury (2005) stated that MIC2 expression is identified in nearly all ESFT and constitutes a useful positive marker when used as part of a panel of immunostains that can help rule out other differential diagnostic considerations. In the present tumor, both of the primary and the nude mouse zenografted tumor tissues express MIC2.…”