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Sarcoma

Sarcomas are rare solid tumors of mesenchymal cell origin with distinct clinical and pathologic features. Based on the origin of the tumor, sarcomas are divided into two categories; sarcomas of soft tissue (e.g., fat, muscle, and connective tissues) and sarcomas of bone. Sarcomas are mostly pediatric tumors accounting for 15% of all childhood malignancies.

Soft tissue sarcomas are heterogeneous group of tumors that are traditionally classified based on histology and tissue type; however, cell origin may not always be clear. Therefore, the identification of genetic alterations along with morphological classification can help clarify diagnosis and classification of soft tissue sarcoma. In general, sarcomas arise from somatic genetic alterations. Nevertheless, national guidelines recommend further genetic assessment if personal and/or family history are suggestive of predisposition to hereditary cancer syndromes.

Sarcoma Test Offering

GenPath Oncology offers four sarcoma FISH assays that maybe used as a confirmatory diagnostic tool in conjunction with both histologic findings and clinical information.

DISEASE STATE FISH ASSAY (on FFPE tissue) CLINICAL UTILITY (Diagnostic) TEST CODE
Alveolar Rhabdomyosarcoma FOXO1 or FKHR (13q14) Gene Rearrangement
  • Translocations involving FOXO1 gene at 13q14 with either the PAX3 or PAX7 genes are characteristics of alveolar rhabdomyosarcoma and not embryonal or pleomorphic rhabdomyosarcoma. Therefore, this FISH assay can assist in differentiating between these subtypes.
  • This FISH assay detects rearrangements at 13q14 regardless of translocation partner.
  • A negative FOXO1 (13q14) rearrangement does not favor a diagnosis of alveolar rhabdomyosarcoma.
 B665-1
Ewing Sarcoma EWSR1 (22q12) Gene Rearrangement
  • EWSR1 (22q12) gene rearrangement is found in a wide variety of Ewing sarcomas such as Ewing sarcoma of the bones, peripheral neuroectodermal tumors (PNET), and Askin tumor. Therefore, rearrangement at 22q12 does not provide a specific sarcoma diagnosis. Diagnosis should be assessed in conjunction with both histologic findings and clinical information.
  • This FISH assay detects rearrangement at 22q12 regardless of translocation partners.
  •  A negative EWSR1 gene rearrangement does not exclude the diagnosis of Ewing sarcoma
 B556-2
Liposarcoma MDM2 (12q15) Gene Amplification
  • MDM2 (12q15) gene amplification is a characteristic of well-differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) and is not seen in benign lipomas. Hence, this FISH assay can be utilized to assist in differentiating between benign lipoma from liposarcomas.
  • Compared to WDLS, DDLS characteristically has higher MDM2 amplification ratio. These differences in MDM2 amplification among liposarcomas may help further define and predict progression to high-grade neoplasia.
 B544-8
Synovial Sarcoma SS18 (18q11.2) Gene Rearrangement
  • SS18 (18q11.2) rearrangement is exclusive to synovial sarcoma, and therefore, can be used to assist in the diagnosis of synovial sarcoma.
  • This FISH assays detects rearrangements at SS18 (18q11.2) regardless of translocation partner.
  • A negative result does not favor the diagnosis of synovial sarcoma.
 J331-0

References:

  1. Amary, M. Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma. Modern Pathology 20, 482–496, 2007.
  2. Ewing sarcoma. NIH U.S. National Library of Medicine. https://ghr.nlm.nih.gov/ condition/ewing-sarcoma. Published November 7, 2017. Accessed November 12, 2017.
  3. Horn, H. Fluorescent in situ analysis of soft tissue tumor associated genetic alterations in formalin-fixed paraffin-embedded tissue. Pathology – Research and Practice 210 (2014) 804-811.
  4. Jain S., Xu R., Prieto VG., Lee P. Molecular classification of soft tissue sarcomas and its clinical applications. International Journal of Clinical and Experimental Pathology. 2010;3(4):416-429
  5. Marshall A., Grosveld G. (2012) Alveolar rhabdomyosarcoma – The molecular drivers of PAX3/7-FOXO1-induced tumorigenesis. doi.org/10.1186/2044-5040- 2-25
  6. Metasystems Product Catalog
  7. NCCN Guidelines Version 2.2018: Soft Tissues Sarcoma. Accessed 7.13.2018
  8. Owosho, A. clinicopathologic study on SS18 fusion positive head and neck synovial sarcomas. Oral Oncology 66 (2017) 46-51.
  9. Przybyl J., Sciot R., Rutkowski P., et al. Recurrent and novel SS18-SSX fusion transcripts in synovial sarcoma: description of three new cases. Tumour Biology. 2012;33(6):2245-2253. doi:10.1007/s13277-012-0486-0.
  10. Patrick L. Ware, Anthony N. Snow, Maya Gvalani, Mark J. Pettenati, Shadi A. Qasem; MDM2 Copy Numbers in Well-Differentiated and Dedifferentiated Liposarcoma: Characterizing Progression to High-Grade Tumors, American Journal of Clinical Pathology, Volume 141, Issue 3, 1 March 2014, Pages 334–341, https://doi.org/10.1309/AJCPLYU89XHSNHQO.
  11. Schmitt-Ney M., Camussi G. (2015) The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway. PLoSONE 10(3): e0121474. https://doi.org/10.1371/journal. pone.0121474.
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