Synovial Sarcoma: Recent Discoveries as a Roadmap to New Avenues for Therapy

Nielsen, Torsten O.; Poulin, Neal; Ladanyi, Marc

doi:10.1158/2159-8290.cd-14-1246

Cited by 144 publications

(145 citation statements)

References 80 publications

(95 reference statements)

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“…16 In synovial sarcomas, there are strong correlations between SSX2 rearrangements and monophasic histology and between SSX1 rearrangements and preference of extremities in tumor location. 15,25,27 In contrast, there is at most modest, if any, prognostic difference between heterogeneous fusion variants (EWSR1-FLI1 type 1 fusion vs others) in Ewing sarcomas. 17,26,28 Notably, few mesenchymal tumor types with specific gene fusions discovered to date do not exhibit typical chromosomal translocations visible at the karyotypic level.…”

Section: Discussionmentioning

confidence: 99%

NAB2–STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors

et al. 2015

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Solitary fibrous tumor (SFT) is characterized by the inv12(q13q13)-derived NAB2-STAT6 fusion, which exhibits variable breakpoints and drives STAT6 nuclear expression. The implications of NAB2-STAT6 fusion variants in pathological features and clinical behavior remain to be characterized in a large cohort of SFTs. We investigated the clinicopathological correlates of this genetic hallmark and analyzed STAT6 immunoexpression in 28 intrathoracic, 37 extrathoracic, and 23 meningeal SFTs. These 88 tumors were designated as histologically nonmalignant in 75 cases and malignant in 13, including 1 dedifferentiated SFT. Eighty cases had formalin-fixed and/or fresh samples to extract assessable RNAs for RT-PCR assay, which revealed NAB2-STAT6 fusion variants comprising 12 types of junction breakpoints in 73 fusion-positive cases, with 65 (89%) falling into 3 major types. The predominant NAB2ex4-STAT6ex2 (n = 33) showed constant breakpoints at the ends of involved exons, whereas the NAB2ex6-STAT6ex16 (n = 16) and NAB2ex6-STAT6ex17 (n = 16) might exhibit variable breakpoints and incorporate NAB2 or STAT6 intronic sequence. Including 73 fusion-positive and 7 CD34-negative SFTs, STAT6 distinctively labeled 87 (99%) SFTs in nuclei, exhibited diffuse reactivity in 73, but did not decorate 98 mimics tested. In seven fusion-negative cases, 6 were STAT6-positive, suggesting rare fusion variants not covered by RT-PCR assay. Regardless of histological subtypes, intrathoracic SFTs affected older patients (P = 0.035) and tended to be larger in size (P = 0.073). Compared with other variants, NAB2ex4-STAT6ex2/4 fusions were significantly predominant in the SFTs characterised by intrathoracic location (Po 0.001), older age (P = 0.005), decreased mitoses (P = 0.0028), and multifocal or diffuse STAT6 staining (P = 0.013), but not found to correlate with disease-free survival. Conclusively, STAT6 nuclear expression was distinctive in the vast majority of SFTs, including all fusion-positive tumors, and exploitable as a robust diagnostics of CD34-negative cases. Despite the associations of NAB2-STAT6 fusion variants with several clincopathological factors, their prognostic relevance should be further validated in large-scale prospective studies of SFTs.

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Section: Discussionmentioning

confidence: 99%

NAB2–STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors

et al. 2015

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“…About 40.0% of synovial sarcomas produce metastasis, most generally in the long bones and lymph nodes [1][2][3] . In this case, there locoregional tumor infiltrating the cervical region.…”

Section: Discussionmentioning

confidence: 99%

“…Synovial sarcomas (SSs) are rare and aggressive neoplasms that account for 5-10% of soft tissue neoplasms 1 , only 3% of which are located in the head and neck region 2 . This neoplasm usually occurs in young adults and is typically found close to the joints of the upper and lower extremities without synovial membrane analysis with hematoxylin and eosin (HE) stained sections was performed at 400X magnification, revealing pleomorphic and oval spindle cells with rounded epithelial cells that formed nests surrounded by fibrous tissue.…”

Section: Introductionmentioning

confidence: 99%

Synovial sarcoma: case report

Ribeiro

Monteiro

Melo

et al. 2017

RGO, Rev. Gaúch. Odontol.

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RESUMOSarcomas sinoviais são neoplasias raras e agressivas, localizadas na região da cabeça e pescoço e geralmente ocorrem em adultos jovens. Relato do caso: este relato apresenta um caso de sarcoma sinovial em um paciente de 15 anos que procurou tratamento médico para sintomas dolorosos e associados à disfagia. A lesão era nodular, extensa, localizada na região da parótida e estendida à região cervical esquerda. O paciente foi tratado em um hospital de referência com um protocolo de tratamento que inicialmente incluiu quimioterapia por seis meses e cirurgia para tentar excisar a lesão, mas a cirurgia foi ineficaz porque a total remoção do tumor poderia comprometer estruturas vitais importantes. A tomografia computadorizada mostrou uma área hipodensa com crescimento difuso, sem envolvimento dos ossos faciais, e a análise histopatológica revelou células fusiformes pleomórficas e ovais, com células epiteliais arredondadas formando ninhos rodeados por tecido fibroso. A análise imunohistoquímica foi conclusiva para o diagnóstico de um sarcoma sinovial de alto grau na região cervical parotídea esquerda. A equipe médica optou pelo tratamento paliativo com radioterapia cervical. O paciente permaneceu hospitalizado por quatro meses após a cirurgia e faleceu 15 meses após o diagnóstico, devido à obstrução das vias aéreas pelo rápido crescimento tumoral residual. O sarcoma sinovial, quando diagnosticado tardiamente pode reduzir a sobrevida dos pacientes por causa de complicações que o crescimento do tumor pode trazer para o prognóstico e qualidade de vida.Termos de indexação: Quimioterapia de indução. Neoplasias. Sarcoma sinovial.

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“…In vitro és in vivo körülmények között szimultán alkalmazott VEGF-gátló és CXCL12/CXCR4 kombináció hatékonyan gátolta a daganatsejtek proliferációját [48]. A Wnt-I-catenin útvonal deregulációja új terápiás célpont lehet [49]. Tumorasszociált antigének (NY-ESO-1, MAGEA4, PRAME, Survivin, SSX) elleni citotoxikus T-lymphocytákkal fázis 1 vizsgálat hamarosan indul (NCT02239861).…”

Section: Kísérleti Szerekunclassified

A sarcoma synoviale kezelési lehetőségei

Deme¹,

Telekes

2015

Orvosi Hetilap

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A sarcoma synoviale a lágyrész-sarcomák 5-10%-ában, az összes malignus daganatok 0,05-0,1%-ában fordul elő. Főként a végtagokon keletkezik, azonban bárhol kialakulhat. A betegek 50%-ában 3-5 éven belül metasztázisok jelennek meg (tüdő, nyirokcsomó, csont), sőt akár 20 év elteltével is számítani lehet a sarcoma synoviale kiújulására. Az 5 éves teljes túlélés lokalizált betegség esetén 76%, metasztatikus esetben 10%. Az életkor, daganatméret, szö-vettani altípus és a radioterápia megtörténte befolyásolja a prognózist. Az adjuváns kemoterápia szerepe nem bizonyított. Számos klinikai vizsgálat van folyamatban a lokálisan előrehaladott, relaptálódott/refrakter és metasztatikus sarcoma synoviale kezelésére. A sarcoma synoviale biológiai viselkedésének jobb megértésével a célzott kezelés és a konvencionális terápia kombinációja válhat a jövő útjává. Orv. Hetil., 2015, 156(22), 875-880.Kulcsszavak: sarcoma synoviale, kemoterápia, radioterápia, célzott kezelés Therapeutic options for synovial sarcomaSynovial sarcomas account for approximately 5 to 10% of soft tissue sarcomas and 0.05 to 0.1% of all malignant neoplasms. They predominantly affect the extremities but can occur in any part of the body. More than 50% of the patients are expected to develop metastatic disease within 3-5 years. In some patients disease recurrence may develop after 20 years. The 5-year overall survival rate is 10% for patients with metastatic disease and 76% for patients with localized one. Age, tumour size, histological subtype, and adjuvant radiotherapy infl uence prognosis. The role of adjuvant chemotherapy has not been proven yet. There are several ongoing clinical trials to determine the effi cacy of active agents used for therapy of locally advanced, relapsed/refractory or metastatic disease. Better understanding of the biological behaviour of synovial sarcomas would provide the future way for the targeted therapy in combination with conventional treatments. Rövidítések CCND1 = ciklin D1; CR = komplett remisszió; DRFS = távoli kiújulásmentes túlélés; EFS = eseménymentes (gyógyszertoxi-citás, -intolerancia, egyéb) túlélés; EpSSG = European Pediatric Soft Tissue Sarcoma Group; HDAC = hiszton-deacetiláz; IGF-1R = inzulinszerű növekedési faktor receptor-1; KT = kemoterápia; LRFS = lokális kiújulásmentes túlélés; MD = metasztatikus betegség; MFS = áttétmentes túlélés; OS = teljes túlélés; PD = progresszív betegség; PFS = progressziómentes túlélés; PR = parciális remisszió; RT = radioterápia; SD = stabil betegség; SEER = Surveillance, Epidemiology, and End Results; SS = sarcoma synoviale A sarcoma synoviale (SS) a ritka malignitások közé tartozik. A malignus daganatok 0,05-0,1%-át és a lágyrész-sarcomák 5-10%-át alkotja [1,2]. Az SS leggyakrabban a serdülőkorúak és fi atal felnőttek 15-40 éves korosztá-lyát érinti, azonban előfordulhat 10 éven aluli gyermekekben, sőt újszülöttekben is [3]. Prognosztikai faktorokTöbb munkacsoport vizsgálta az SS-ben szenvedő pá-ciensek túlélését befolyásoló prognosztikai faktorokat, amelyek közül az 5 cm vagy ann...

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Synovial Sarcoma: Recent Discoveries as a Roadmap to New Avenues for Therapy

Cited by 144 publications

References 80 publications

NAB2–STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors

NAB2–STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors

Synovial sarcoma: case report

A sarcoma synoviale kezelési lehetőségei

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