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Doctoral Thesis
DOI
10.11606/T.5.2007.tde-20082007-162629
Document
Author
Full name
Maria Fernanda Carriel Amary
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Bernardi, Fabiola Del Carlo (President)
Alves, Maria Teresa de Seixas
Bacchi, Carlos Eduardo
Camargo, Olavo Pires de
Próspero, José Donato de
Title in Portuguese
Detecção da fusão SS18-SSX em material parafinado e comparação de métodos moleculares como ferramentas no diagnóstico do Sarcoma Sinovial
Keywords in Portuguese
Biologia molecular
Fluorêscencia em hibridização in situ
Reação em cadeia da polimerase via transcriptase reversa
Sarcoma
Sarcoma sinovial
Abstract in Portuguese
O Sarcoma Sinovial revela consistentemente t(X;18) resultando em SS18- SSX1, SS18-SSX2 e raramente SS18-SSX4. Dos 328 casos incluídos neste estudo, Sarcoma Sinovial foi considerado a primeira possibilidade diagnóstica ou um importante diagnóstico diferencial em 134 casos: destes, cDNA de qualidade foi obtido em 131. A fusão SS18-SSX foi identificada em 126 (96%) casos (74 SS18-SSX1, 52 SS18-SSX2) através de qRT-PCR e 120 (92%) por RT-PCR convencional. 101 casos no array de tecidos, analisados por FISH, revelaram que 87 (86%) mostraram rearranjo do SS18. Quatro casos positivos por RT-PCR mostraram perda de um sinal spectrum green e 15 casos revelaram cópias múltiplas de SS18: ambos os achados são potencialmente problemáticos na interpretação de resultados. Um dos 3 casos não analisados por RT-PCR por não ter gerado cDNA de qualidade, foi positivo por FISH. A fusão SS18-SSX1 foi demonstrada em 56 SS monofásicos e 18 SS bifásicos. SS18-SSX2 foi detectada em 41 monofásicos e 11 bifásicos. Áreas pouco diferenciadas foram identificadas em 44 casos (31%). Não houve correlação estatisticamente significante entre os subtipos bifásico, monofásico e o tipo de fusão. Cinco casos foram negativos através dos três métodos utilizados, três de localização pleural. Após correlação clínica, o diagnóstico de mesotelioma foi favorecido em um caso, tumor fibroso solitário em outro e o diagnóstico de sarcoma sem outras especificações no terceiro. A possibilidade do diagnóstico de TMBNP não pode ser excluída nos outros dois casos. Nós concluímos que os métodos moleculares são ferramentas auxiliares importantes para o diagnóstico de SS com 95% de sensibilidade e 100% de especificidade, mas os resultados devem ser interpretados à luz de características clínicas e dados imunohistoquímicos.
Title in English
Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded tissue and comparison of molecular methods as diagnostic tools for Synovial Sarcoma
Keywords in English
In situ hybridization fluorescence
Molecular biology
Reverse transcriptase polymerase chain reaction
Sarcoma
Sarcoma synovial
Abstract in English
Synovial Sarcoma consistently harbors t(X;18) resulting in SS18-SSX1, SS18-SSX2 and rarely SS18-SSX4 fusion transcripts. Of 328 cases included in our study, synovial sarcoma was either the primary diagnosis or was very high in the differential diagnosis in 134 cases: of these, amplifiable cDNA was obtained from 131. SS18-SSX fusion products were found in 126 (96%) cases, (74 SS18-SSX1, 52 SS18-SSX2), using quantitative and 120 by conventional RT-PCR. 101 cases in a tissue microarray, analyzed by FISH, revealed that 87 (86%) showed SS18 rearrangement: 4 reverse transcriptase polymerase chain reaction positive cases, reported as negative for FISH, showed loss of one spectrum green signal, and 15 cases had multiple copies of the SS18 gene: both findings are potentially problematic when interpreting results. One of 3 cases, not analyzed by RT PCR due to poor quality RNA, was positive by FISH. SS18-SSX1 was present in 56 monophasic and 18 biphasic synovial sarcoma: SS18-SSX2 was detected in 41 monophasic and 11 biphasic synovial sarcoma. Poorly differentiated areas were identified in 44 cases (31%). There was no statistically significant association between biphasic, monophasic and fusion type. Five cases were negative for SS18 rearrangement by all methods, 3 of which were pleural-sited neoplasms. Following clinical input, a diagnosis of mesothelioma was favored in one case, a sarcoma, not-otherwise specified in another and a solitary fibrous tumor in the third case. The possibility of a malignant peripheral nerve sheath tumor could not be excluded in the other 2 cases. We concluded that the employment of a combination of molecular approaches is a powerful aid to diagnosing synovial sarcoma giving at least 96% sensitivity and 100% specificity but results must be interpreted in the light of other modalities such as clinical findings and immunohistochemical data.
 
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Publishing Date
2007-08-22
 
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