Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica

Detalhes bibliográficos
Autor(a) principal: Herbst, Thiago Eugenio Gouveia [UNESP]
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://hdl.handle.net/11449/132609
http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/18-12-2015/000855647.pdf
Resumo: Histiocytic sarcoma (HS) is a malignant neoplasm characterized by the proliferation of large cells that have morphological and immunophenotypic features similar to mature tissue histiocytes. It is a rare neoplasm, accounting for less than 1% of non-Hodgkin lymphomas. This rarity is partly explained by the difficulties in its diagnostic and morphological characterization, since it is confused with other pleomorphic malignant neoplasms. The objectives of this study were to evaluate changes in genomic gains and losses using the comparative genomic hybridization technique (CGH-array), microRNA profile (miRNA) evaluation, determine the principal morphological criteria and immunohistochemical markers (IMH) that could define this entity, and identify entities that can mistakenly lead to underdiagnosis. To achieve this, 7,600 pathology reports were reviewed and, of these, 47 possible cases of HS with nodal presentation were selected. Four cases with an established diagnosis of HS were also included in the analysis. Twelve morphological criteria and 5 IMH markers were evaluated. Among the 47 cases, 7 cases of HS were identified that had initially been diagnosed as undifferentiated metastatic neoplasm (undifferentiated carcinoma) or metastatic melanoma. The IMH markers that were most efficient for complementary diagnosis were CD163 and CD68. Evaluation of the profiles of 377 miRNAs showed clustering of 51 miRNA compared with the control; 44 were hypoexpressed and 7 were hyperexpressed and the most relevant were: miR-486-5p, miR-92a, miR-15b-5p (hyporegulated); and miR-10b-5p, miR-455-5p and miR-19 (hyperexpressed). These miRNA are involved in apoptosis, cell growth and proliferation pathways. The main genes involved in pathogenesis and candidates for validation in future studies are: ERBB2, TGFB1, TNF (activated); and TP53 and PD98059 (inhibited). These genes may represent future therapeutic targets. The CGH-array proved to be unfeasible in ...
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spelling Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímicaSarcoma histiocíticoLinfomaImunohistoquímicaExpressão gênicaMorfologiaLymphomasHistiocytic sarcoma (HS) is a malignant neoplasm characterized by the proliferation of large cells that have morphological and immunophenotypic features similar to mature tissue histiocytes. It is a rare neoplasm, accounting for less than 1% of non-Hodgkin lymphomas. This rarity is partly explained by the difficulties in its diagnostic and morphological characterization, since it is confused with other pleomorphic malignant neoplasms. The objectives of this study were to evaluate changes in genomic gains and losses using the comparative genomic hybridization technique (CGH-array), microRNA profile (miRNA) evaluation, determine the principal morphological criteria and immunohistochemical markers (IMH) that could define this entity, and identify entities that can mistakenly lead to underdiagnosis. To achieve this, 7,600 pathology reports were reviewed and, of these, 47 possible cases of HS with nodal presentation were selected. Four cases with an established diagnosis of HS were also included in the analysis. Twelve morphological criteria and 5 IMH markers were evaluated. Among the 47 cases, 7 cases of HS were identified that had initially been diagnosed as undifferentiated metastatic neoplasm (undifferentiated carcinoma) or metastatic melanoma. The IMH markers that were most efficient for complementary diagnosis were CD163 and CD68. Evaluation of the profiles of 377 miRNAs showed clustering of 51 miRNA compared with the control; 44 were hypoexpressed and 7 were hyperexpressed and the most relevant were: miR-486-5p, miR-92a, miR-15b-5p (hyporegulated); and miR-10b-5p, miR-455-5p and miR-19 (hyperexpressed). These miRNA are involved in apoptosis, cell growth and proliferation pathways. The main genes involved in pathogenesis and candidates for validation in future studies are: ERBB2, TGFB1, TNF (activated); and TP53 and PD98059 (inhibited). These genes may represent future therapeutic targets. The CGH-array proved to be unfeasible in ...O Sarcoma Histiocítico (SH) é uma neoplasia maligna caracterizada pela proliferação de células grandes que possuem aspecto morfológico e imunofenotípico semelhantes ao histiócito maduro tecidual. É uma neoplasia rara, perfazendo menos que 1% dos Linfomas Não-Hodgkin. Tal raridade pode ser explicada pela dificuldade de sua caracterização diagnóstica e morfológica, confundindo-se com outras neoplasias malignas pleomórficas. Os objetivos do presente estudo são: avaliar alterações no padrão de ganhos e perdas genômicas pela técnica de Hibridação Genômica Comparativa (CGH-array), avaliação do perfil de MicroRNA (miRNA), apontar os principais critérios morfológicos e marcadores imunoistoquímicos (IMH) que venham a definir esta entidade e identificar quais entidades que erroneamente podem levar a subdiagnostico.Para tanto, foram revisados 7.600 laudos anatomopatológicos e, destes, foram selecionados 47 casos possíveis de SH, com apresentação nodal. Somando-se a estes, quatro casos sabidamente com diagnóstico de SH foram incluídos na análise. Foram avaliados 12 critérios morfológicos e 05 marcadores IMH. Dos 47 casos, foram localizados 07 SH, cujo diagnóstico inicial foi de neoplasia indiferenciada metastática (carcinoma indiferenciado) ou melanoma metastático. Os marcadores IMH que se mostraram mais eficientes para complementação diagnóstica foram CD163 e CD68. A avaliação do perfil de 377 miRNAs demonstrou clusterização de 51 miRNA, quando comparado ao controle, sendo 44 hipoexpresssos e 07 hiperexpressos, sendo os mais relevantes: miR-10b-5p, miR-455-5p e miR-19 (hiperexpressos); miR-486-5p, miR-92a, miR-15b-5p (hiporegulados). Tais miRNA estão envolvidos nas vias da apoptose, crescimento e proliferação celular. Os principais genes envolvidos na patogenia e candidatos a validação com futuros estudos são: ERBB2, TGFB1,TNF(ativados) e TP53 e PD98059 (inibidos).Tais genes podem corresponder a futuros...Universidade Estadual Paulista (Unesp)Domingues, Maria Aparecida Custódio [UNESP]Universidade Estadual Paulista (Unesp)Herbst, Thiago Eugenio Gouveia [UNESP]2016-01-13T13:27:19Z2016-01-13T13:27:19Z2015-02-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis75 f.application/pdfHERBST, Thiago Eugenio Gouveia. Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica. 2015. 75 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2015.http://hdl.handle.net/11449/132609000855647http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/18-12-2015/000855647.pdf33004064056P50585723113037140Alephreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPporinfo:eu-repo/semantics/openAccess2024-09-03T19:03:32Zoai:repositorio.unesp.br:11449/132609Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T19:03:32Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
title Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
spellingShingle Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
Herbst, Thiago Eugenio Gouveia [UNESP]
Sarcoma histiocítico
Linfoma
Imunohistoquímica
Expressão gênica
Morfologia
Lymphomas
title_short Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
title_full Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
title_fullStr Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
title_full_unstemmed Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
title_sort Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica
author Herbst, Thiago Eugenio Gouveia [UNESP]
author_facet Herbst, Thiago Eugenio Gouveia [UNESP]
author_role author
dc.contributor.none.fl_str_mv Domingues, Maria Aparecida Custódio [UNESP]
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Herbst, Thiago Eugenio Gouveia [UNESP]
dc.subject.por.fl_str_mv Sarcoma histiocítico
Linfoma
Imunohistoquímica
Expressão gênica
Morfologia
Lymphomas
topic Sarcoma histiocítico
Linfoma
Imunohistoquímica
Expressão gênica
Morfologia
Lymphomas
description Histiocytic sarcoma (HS) is a malignant neoplasm characterized by the proliferation of large cells that have morphological and immunophenotypic features similar to mature tissue histiocytes. It is a rare neoplasm, accounting for less than 1% of non-Hodgkin lymphomas. This rarity is partly explained by the difficulties in its diagnostic and morphological characterization, since it is confused with other pleomorphic malignant neoplasms. The objectives of this study were to evaluate changes in genomic gains and losses using the comparative genomic hybridization technique (CGH-array), microRNA profile (miRNA) evaluation, determine the principal morphological criteria and immunohistochemical markers (IMH) that could define this entity, and identify entities that can mistakenly lead to underdiagnosis. To achieve this, 7,600 pathology reports were reviewed and, of these, 47 possible cases of HS with nodal presentation were selected. Four cases with an established diagnosis of HS were also included in the analysis. Twelve morphological criteria and 5 IMH markers were evaluated. Among the 47 cases, 7 cases of HS were identified that had initially been diagnosed as undifferentiated metastatic neoplasm (undifferentiated carcinoma) or metastatic melanoma. The IMH markers that were most efficient for complementary diagnosis were CD163 and CD68. Evaluation of the profiles of 377 miRNAs showed clustering of 51 miRNA compared with the control; 44 were hypoexpressed and 7 were hyperexpressed and the most relevant were: miR-486-5p, miR-92a, miR-15b-5p (hyporegulated); and miR-10b-5p, miR-455-5p and miR-19 (hyperexpressed). These miRNA are involved in apoptosis, cell growth and proliferation pathways. The main genes involved in pathogenesis and candidates for validation in future studies are: ERBB2, TGFB1, TNF (activated); and TP53 and PD98059 (inhibited). These genes may represent future therapeutic targets. The CGH-array proved to be unfeasible in ...
publishDate 2015
dc.date.none.fl_str_mv 2015-02-26
2016-01-13T13:27:19Z
2016-01-13T13:27:19Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv HERBST, Thiago Eugenio Gouveia. Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica. 2015. 75 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2015.
http://hdl.handle.net/11449/132609
000855647
http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/18-12-2015/000855647.pdf
33004064056P5
0585723113037140
identifier_str_mv HERBST, Thiago Eugenio Gouveia. Sarcoma histiocítico: análise molecular pela técnica de hibridação genômica comparativa, microRNA e imunoistoquímica. 2015. 75 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2015.
000855647
33004064056P5
0585723113037140
url http://hdl.handle.net/11449/132609
http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/18-12-2015/000855647.pdf
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv 75 f.
application/pdf
dc.publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.source.none.fl_str_mv Aleph
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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