Soft tissue tumors: Synovial sarcoma

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Soft tissue tumors: Synovial sarcoma

Identity

Other names t(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 SYT (Synovial tumor)

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, SSX2, SSX4 (one case) (Synovial Sarcoma X)

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%)

External links

Orphanet Synovialosarcoma

Bibliography

Translocations involving the X chromosome in solid tumors : presentation of two sarcomas with t(X ;18)(q13,p11).

Limon J, Dal Cin P, Sandberg AA.

Cancer Genet Cytogenet 1986; 23: 87-91.

Translocation X ;18 in synovial sarcoma.

Turc-Carel C, Dal Cin P, Limon J, Li F, Sandberg AA .

Cancer Genet Cytogenet 1986; 23: 93.

A consistent chromosome translocation in synovial sarcoma.

Smith S, Reeves BR, Wong L, Fisher C.

Cancer Genet Cytogenet 1987; 26: 179-180.

Translocation (X;18) in a synovial sarcoma.

Griffin CA, Emanuel BS.

Cancer Genet Cytogenet 1987; 26: 181-183.

Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma.

Turc-Carel C, Dal Cin P, Limon J, Rao U, Li PF, Corson JM, Zimmerman R, Parry DM, Cowan JM, Sandberg AA.

Proc Natl Acad Sci USA 1987; 84: 1981-1985.

Cytogenetics of synovial sarcoma: presentation and review of the literature

Limon J, Mrozek K, Mandahl N, Nedoszytko B, Verhest A, Rys J, Niezabitowski A, Babinska M, Nosek H, Ochalek T, Kopacz A, Willen H, Rydholm A, Heim S, Mitelman F.

Genes Chromosom Cancer 1991; 3: 338-345.

Mediastinal synovial sarcoma with t(X;18).

Le Marc'hadour F, Pasquier B, Leroux D, Jacrot M.

Cancer Genet Cytogenet 1991; 55: 265-267.

Chromosomes in the diagnosis of soft tissue tumors. I. Synovial sarcoma.

Dal Cin P, Rao U, Jani-Sait S, Karakousis C, and Sandberg AA.

Modern Pathol 1992; 5: 357-362.

Localization of the synovial sarcoma t(X ;18)(p11.2 ;q11.2) breakpoint by fluorescent in situ hybridization.

Knight JC, Reeves BR, Keaney L, Monaco P, Lehrach H, Cooper CS.

Hum Mol Genet 1992; 1: 633-637.

Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18) (p11.2 ;q11.2)breakpoint.

de Leeuw B, Berger W, Sinke RF, Gilgenkrantz S, Geraghty MT, Valle D, Monaco AP, Lehrach H, Ropers HH, Geurts van Kessel A.

Genes Chromosom Cancer 1993; 6: 182-189.

Sublocalization of the synovial sarcoma-associated t(X;18) chromosomal breakpoint in Xp11.2 using cosmid cloning and fluorescence in situ hybridization.

de Leeuw B, Suijkerbuijk RF, Balemans M, Sinke RF, de Jong B, Molenaar WM, Meloni AM, Sandberg AA, Geraghty M, Hofker M, Ropers HH, Geurts van Kessel A.

Oncogene 1993; 8: 1457-1463.

The t(X ;18)(p11.2 ;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome.

Shipley JM, Clark J, Crew AJ, Birdsall S, Rocques PJ, Chelly J, Monaco AP, Abe S, Gusterson BA, Cooper SS.

Oncogene 1994; 9: 1447-1453.

Distinct Xp11.2 breakpoint H: relationship to histologic subtypes.

de Leeuw B, Suijkerbuijk RF, Olde Weghuis D, Meloni AM, Stenman G, Kindblom LG, Balemans M, van den Berg E, Molenaar WM, Sandberg AA, Geurts van Kessel A.

Cancer Genet Cytogenet 1994; 73: 89-94.

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 JM, Chan AML, Gusterson BA, Cooper CS.

Nature genetics 1994; 7: 502-508.

Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma.

Shipley JM, Crew AJ, Birdsall S, Gill S, Clark J, Fisher C, Kelsey A, Nojima T, Sonobe H, Cooper SS, Gusterson BA.

Am J Pathol 1996; 148(2): 559-567.

SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma.

Kaxai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, and Ladanyi M.

N Engl J Med 1998;338: 153-160.

Masked t(X;18)(p11:q11) in a biphasic synovial sarcoma revealed by FISH and RT-PCR.

Geurts van Kessel A, de Bruijn D, Hermsen L, Janssen I, dos Santos NR, Willems R, Makkus L, Schreuder H, Veth R.

Genes Chromosom Cancer 1998; 23: 198-201.

Synovial sarcoma (review article).

Fisher C.

Ann Diag Pathol 1998; 2: 401-421.

A novel fusion gene, SYT-SSX4, in synovial sarcoma.

Skytting B, Nilsson G, Brodin B, Xie Y, Lundeberg J, Uhlen M, Larsson O.

J Nat Cancer Inst 1999; 91: 974-975.

Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma.

van de Rijn M, Barr FG, Collins MH, Xiong QB, Fisher C.

Am J Clin Pathol 1999;112: 43-49.

The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome.

Nilsson G, Skytting B, Xie Y, Brodin B, Perfekt R, Mandahl N, Lundeberg J, Uhlen M, andLarsson O.

Cancer Res 1999; 59: 3180-3184.

Synovial sarcoma: report of a serie of 25 consecutive children from a single institution.

Ferrari A, Casanova M, Massimino M, Luksch R, Cefalo G, Lombardi F, Galimberti S, Riganti G, and Fossati-Bellani F.

Med Ped Oncol 1999; 32: 32-37.

Synovial sarcoma. Identification of low and high risk groups.

Bergh P, Meis- Kindblom JM, Gherlinzoni F, Berlin O, Bacchini P, Bertoni F, Gunterberg B, Kindblom LG.

Cancer 1999; 85: 2596-2607.

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Contributor(s)

Written 02-2000 Christine Pérot

Citation

This paper should be referenced as such :
Pérot C . Soft tissue tumors: Synovial sarcoma. Atlas Genet Cytogenet Oncol Haematol. February 2000 .
URL : http://AtlasGeneticsOncology.org/Tumors/SynovSarcID5044.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Apr 17 14:14:52 2008

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For comments and suggestions or contributions, please contact us

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Other names	t(X;18)(p11.2;q11.2) in synovial sarcoma


	t(X;18)(p11.2;q11.2) in synovial sarcoma G-banding - Courtesy Charles Bangs

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 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

Gene Name	SYT (Synovial tumor)
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, SSX2, SSX4 (one case) (Synovial Sarcoma X)
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

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%)

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed