Ewing Sarcoma (EWS) 22q12 Rearrangement, FISH, Tissue
Supporting the diagnosis of Ewing sarcoma (EWS)/primitive neuroectodermal tumor (PNET), myxoid chondrosarcoma, desmoplastic small, round cell tumor, clear cell sarcoma, and myxoid liposarcoma when used in conjunction with an anatomic pathology consultation
An aid in the diagnosis of EWS when reverse transcriptase-PCR results are equivocal or do not support the clinical picture
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Ewing sarcoma (EWS)/primitive neuroectodermal tumors (PNET) are members of the small, round cell group of tumors that are thought to originate in cells of primitive neuroectodermal origin with variable degrees of differentiation. The small, round cell group of tumors also includes rhabdomyosarcomas, desmoplastic small, round cell tumors, and poorly differentiated synovial sarcomas. Although immunohistochemical markers can be helpful in the correct diagnosis of these tumors, recent molecular studies have shown the specificity of molecular markers in differentiating specific subtypes of small, round blue-cell tumors. Accurate diagnosis of each tumor type is important for appropriate clinical management of patients.
Ewing tumors are characterized cytogenetically by rearrangements of the EWSR1 gene at 22q12 with FLI1 at 11q24 (t[11;22]) or ERG at 21q22 (t[21;22]) in 85% and 5% to 10% of Ewing tumors, respectively. Less than 1% of cases may have other fusion partners such as ETV1 at 7p22, E1AF at 17q12, or FEV at 2q33. Detection of these transcripts by reverse transcriptase-PCR (RT-PCR) (83363 Ewing Sarcoma/Primitive Neuroectodermal Tumors (ES/PNET) by Reverse Transcriptase PCR (RT-PCR), Paraffin) that allows specific identification of the t(11;22) and the t(21;22), has greatly facilitated the diagnosis of Ewing tumors. However, if the quality of the available RNA is poor, the results are equivocal, or if a rare translocation partner is present, FISH testing has proven to be useful in identifying the 22q12 EWS gene rearrangement in these tumors.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the EWSR1 FISH probe set.
A positive result is consistent with a diagnosis of Ewing sarcoma (EWS)/primitive neuroectodermal tumors (PNET).
A negative result suggests that a EWSR1 rearrangement is not present but does not exclude the diagnosis of EWS/PNET.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA and is best used as an adjunct to existing clinical and pathologic information.
Fixatives other than formalin (eg, Prefer, Bouin's) may not be successful for FISH assays. Although FISH testing will not be rejected due to non-formalin fixation results may be compromised.
Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.
FISH analysis was performed on 38 formalin-fixed, paraffin-embedded tissue samples, 16 tumors, and 22 noncancerous control specimens. The normal controls were used to generate a normal cutoff for this assay. Rearrangement of EWSR1 was identified in 14 tumor specimens and 2 yielded no results due to poor hybridization.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Ushigome S, Machinami R, Sorensen PH: Chapter XIV: Ewing sarcoma/Primitive neuroectodermal tumour (PNET). In World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Soft Tissue and Bone. Edited by CDM Fletcher, KK Unni, F Mertens. Lyon, IARC Press, 2002, pp 298-300
2. Burchill SA: Ewing's sarcoma: diagnostic, prognostic, and therapeutic implications of molecular abnormalities. J Clin Pathol 2003 February;56(2):96-102
3. Riley RD, Burchill SA, Abrams KR, et al: A systematic review of molecular and biological markers in tumors of the Ewing's sarcoma family. Eur J Cancer 2003 January;39:19-30