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Soft Tissues: Synovial sarcoma with t(X;18)(p11;q11) SS18/

Written2000-02Christine Pérot
Laboratoire de Cytogenetique, Hopital Saint-Antoine, Paris, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 9040/3 Synovial sarcoma, NOS
Atlas_Id 5044
Phylum Soft Tissues::Synovial sarcoma
Other namest(X;18)(p11.2;q11.2) in synovial sarcoma
t(X;18)(p11.2;q11.2) in synovial sarcoma G-banding - Courtesy Charles Bangs

Clinics and Pathology

Epidemiology rare soft tissue tumor, it accounts for up to 5 to 8% of soft tissue sarcomas , the fourth most common type of sarcoma after malignant fibrous histyocytoma, liposarcoma and rhabdomyosarcoma ; the most common pediatric non rhabdomyosarcomatous soft tissue cancer; average incidence : 2,75 per 100000 population based on a canandian study
Clinics most prevalent in adolescents and young adults, it occurs primarily in the para-articular regions of the extremities, especially the lower ones; rarely, it is encountered in various areas such as parapharyngeal region, abdominal wall, lung or cardiac tissue, ä
Pathology well-defined, apparently unrelated to synovium (cf various rare localisations), it displays characteristics of concurrent epithelial and spindle cell proliferation; several types are recognized : two major ones:
  • biphasic, with epithelial and spindle cell components in various proportions and
  • monophasic fibrous type;
  • monophasic epithelial type is much less common ;
  • may also present as a poorly differentiated small cell neoplasm; diagnosis may be difficult especially for the two later.
    in general, very few problems in diagnosis in the biphasic type, may be not ascertained in some instances even after immunohistochemical examination
    • Treatment complete surgical excision of the primary tumor is actually the basis of the treatment; the optimal treatment approach is to be determined as post operative radiotherapy and adjuvant chemotherapy may permit limb preserving surgery and limit local recurrence and (micro) metastasis disease (lung+++)
    Prognosis
  • traditionnally has had a bad prognosis whateither the biphasic or monophasic type, poorer in the poorly differentiated small cell neoplasm.
  • EFS at 5 years : 45-60%; improved in a recent german study to 74% for children and adolescents; improvements in adults too
  • recents prognostic studies to identify risk groups and adequate treatment strategies indicate that synovialosarcomas might not be uniformely high grade tumors

    • Cytogenetics

    Cytogenetics
    Morphological    		 a t(X;18)(p11.2;q11.2) is found in almost all synovial sarcomas (8O%) whatsoever the histologic type may be; t(X ;18)(p11.2 ;q11.2) seems to be specific : it is not found in other spindle cell sarcomas, and very rarely detected in other tumors as malignant fibrous histyocytoma or fibrosarcomas
    Cytogenetics Molecular detectable by metaphasic and/or interphasic dual colour fluorescent in situ cytogenetics; hybridization combining centomere X or 18 probes with respectively 18 or X whole chromosome painting or YAC probes both numerical and structural anomalies are found in 50% of cases, numerical anomalies only in 20% (+7,+8,+12,+21,-3, -11, -14, -22) and structural.anomalies only in 20% (involving chromosomes 1, 3, 11, 12, 15, 17 and 21: tumors may be hypodiploid, pseudodiploid, hyperdiploid or near tetraploid without a common pattern; DNA flow cytometry study revealed poorer prognosis for aneuploid tumors
    Variants a few variants have been described, involving chromosomes 1, 3, 15 or 21, ...; masked translocations were identified as t(5 ;18), t(X ;7) without chromosome X or 18 apparent involvement respectively

    Genes involved and Proteins

    Gene Name SS18
    Location 18q11.2
    Dna / Rna 3,7 kb mRNA
    Protein 387 amino acids; glutamin, prolin and glycin rich; three potential SH2 binding domains and one SH3; widely expressed, limited to cartlagenous and nervous tissues in early embryonal development; biological properties still unknown

    Gene Name SSX1
    Location Xp11.2
    Dna / Rna 1,6 kb mRNA
    Protein 188 amino acids; 81% homologie for SSX1 and SSX2; Kruppel associated box (KRAB) homology; restricted expression to testis and thyroid; biological properties still unknown

    Result of the chromosomal anomaly

    Hybrid Gene
    Description 5 prime SYT- 3 prime SSX1/2
    Fusion Protein
    Description substitution of the 8 last amino acids of SYT by 78 amino acids of SSX, with exclusion of KRAB and one SH2 domain
    Oncogenesis
  • the important role is that of the transcript situated on the der(X)
  • RT-PCR diagnosis : ther eis a correlation between biphasic type and SYT/SSX1 variant (where SSX2 involvement is never detected), SYT/SSX2 is more common than SYT/SSX1 in monophasic one
  • SYT/SSX1 variant might be less favorable, associated with higher tumor proliferating rate and reduced overall survival (metastasis free survival 42% vs 80%)
    •   

    Bibliography

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    Cancer. 1999 ; 85 (12) : 2596-2607.
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    Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma.
    Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, Gusterson BA, Cooper CS
    Nature genetics. 1994 ; 7 (4) : 502-508.
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    The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome.
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    Citation

    This paper should be referenced as such :
    Prot, C
    Soft tissue tumors: Synovial sarcoma
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(2):88-90.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/SynovSarcID5044.html

    Other genes implicated (Data extracted from papers in the Atlas) [ 14 ]

    Genes ATF2 CPM CRK HTRA2 KCNH1 MIR183 PAEP SNAI1 SRSF3 SS18
    SS18 SS18L1 SSX2 YBX1

    Translocations implicated (Data extracted from papers in the Atlas)

     t(X;18)(p11;q11) SS18/

    External links

    Mitelman database t(X;18)(p11;q11) SS18/ [Case List]    t(X;18)(p11;q11) SS18/ [Association List] Mitelman database (CGAP - NCBI)
    arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
     
     
    Disease databaseSoft Tissues: Synovial sarcoma with t(X;18)(p11;q11) SS18/
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


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    indexed on : Fri Jun 30 11:25:12 CEST 2017

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