Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides

Detalhes bibliográficos
Autor(a) principal: Cardili, Leonardo [UNIFESP]
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5425903
http://repositorio.unifesp.br/handle/11600/50477
Resumo: Introduction. Spitzoid tumors represent a heterogeneous group of melanocytic neoplasms. In recent years, several advances in Molecular Biology afforded significant discoveries on the pathogenesis and the biological behavior of these tumors. The BAP1 inactivation, the presence of kinase fusion related-proteins and the role of p16 protein are among the main criteria launched by new classification proposals and represent innovative markers with potential clinical significance. Objetive. To evaluate the immunohistochemical expression of BAP1, ALK, ROS1 and p16 proteins in spitzoid tumors. Methods. Retrospective study based on 47 tissue samples fixed in formalin and embedded in paraffin. This series was composed by the Pathology archives of three cancer reference institutions in the state of São Paulo, Brazil. Clinical-demographic data, histopathological aspects and immunohistochemical results for BAP1, ALK, ROS1 and p16 were studied in this case series composed by 27 Spitz nevus (NS), 15 Atypical Spitzoid Tumors (AST) and 5 Spitzoid Melanomas (MS). Results. Medium age was 21.2 years. Medium histological tumoral width was 5.7 millimeters. We observed statistical significance between diagnostic categories and age, width, mitotic index, ulceration, atypia, loss of maturation and the presence of giant cells. The global frequency of BAP1- inactivated tumors was 4.3% (02/46), both of them AST. The proportional frequency of BAP1-inactivated cases in AST group was 14.2% (02/14). We found no immunostaining for ALK and ROS1 in any out of 47 studied cases. We also did not observe a statistically significant correlation between loss of immunoexpression of p16 and non-benign categories. Conclusions. Age, width and mitotic index were significant diagnostic criteria to differentiate between MS and the remaining categories. Ulceration, atypia, loss of maturation and the presence of giant cells were significant diagnostic criteria to differentiate benign lesions (NS) and non-benignlesions (AST and MS). The loss of nuclear immunoexpression of BAP1 was exclusive to the AST category. We did not observe immunoexpression of ALK or ROS1 in any case. The immunohistochemical evaluation of p16 protein did not allowed differentiation between benign tumors (NS) and non-benign tumors (AST and MS).
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spelling Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoidesImmunoexpression of BAP1, ALK, ROS1 e p16 in spitzoid tumorsSpitzoidBAP1ROS1ALKP16Nevus, epithelioid and spindle cellImmunohistochemistryNevus, pigmentedSpitzoideBAP1ROS1ALKP16Nevo de células epitelioides e fusiformesImuno-histoquímicaNevo pigmentadoIntroduction. Spitzoid tumors represent a heterogeneous group of melanocytic neoplasms. In recent years, several advances in Molecular Biology afforded significant discoveries on the pathogenesis and the biological behavior of these tumors. The BAP1 inactivation, the presence of kinase fusion related-proteins and the role of p16 protein are among the main criteria launched by new classification proposals and represent innovative markers with potential clinical significance. Objetive. To evaluate the immunohistochemical expression of BAP1, ALK, ROS1 and p16 proteins in spitzoid tumors. Methods. Retrospective study based on 47 tissue samples fixed in formalin and embedded in paraffin. This series was composed by the Pathology archives of three cancer reference institutions in the state of São Paulo, Brazil. Clinical-demographic data, histopathological aspects and immunohistochemical results for BAP1, ALK, ROS1 and p16 were studied in this case series composed by 27 Spitz nevus (NS), 15 Atypical Spitzoid Tumors (AST) and 5 Spitzoid Melanomas (MS). Results. Medium age was 21.2 years. Medium histological tumoral width was 5.7 millimeters. We observed statistical significance between diagnostic categories and age, width, mitotic index, ulceration, atypia, loss of maturation and the presence of giant cells. The global frequency of BAP1- inactivated tumors was 4.3% (02/46), both of them AST. The proportional frequency of BAP1-inactivated cases in AST group was 14.2% (02/14). We found no immunostaining for ALK and ROS1 in any out of 47 studied cases. We also did not observe a statistically significant correlation between loss of immunoexpression of p16 and non-benign categories. Conclusions. Age, width and mitotic index were significant diagnostic criteria to differentiate between MS and the remaining categories. Ulceration, atypia, loss of maturation and the presence of giant cells were significant diagnostic criteria to differentiate benign lesions (NS) and non-benignlesions (AST and MS). The loss of nuclear immunoexpression of BAP1 was exclusive to the AST category. We did not observe immunoexpression of ALK or ROS1 in any case. The immunohistochemical evaluation of p16 protein did not allowed differentiation between benign tumors (NS) and non-benign tumors (AST and MS).Introdução. Tumores spitzoides compõem um grupo heterogêneo de neoplasias melanocíticas. Nos últimos anos, avanços no campo da biologia molecular possibilitaram descobertas significativas sobre a patogênese e o comportamento biológico desses tumores. A inativação de BAP1, a presença de proteínas relacionadas a translocações em genes codificadores de tirosinoquinases e a função da proteína p16 estão dentre os critérios utilizados por novas propostas de classificação e representam marcadores com potencial significado clínico. Objetivo. Avaliar a expressão imuno-histoquímica das proteínas BAP1, ALK, ROS1 e p16 em tumores spitzoides. Metodologia. Estudo retrospectivo baseado em 47 amostras de tecido fixado em formol e incluído em parafina. A composição da casuística contou com a contribuição dos arquivos de três instituições de referência oncológica no estado de São Paulo, Brasil. Dados clínico-demográficos, aspectos histopatológicos e reatividade imuno-histoquímica para BAP1, ALK, ROS1 e p16 foram analisados em uma série composta por 27 nevos de Spitz (NS), 15 tumores spitzoides atípicos (AST) e 5 melanomas spitzoides (MS). Resultados. A média etária foi de 21,2 anos. O tamanho tumoral médio foi de 5,7 milímetros. Foi observada significância estatística entre as categorias diagnósticas e as variáveis idade, tamanho, índice mitótico, ulceração, atipia, perda de maturação e presença de células gigantes. A frequência geral de casos BAP1-inativados foi 4,3% (02/46), ambos pertencentes à categoria AST. A frequência proporcional de casos BAP1-inativados da categoria AST foi de 14,2% (02/14). Em relação aos anticorpos ALK e ROS1, não foi observada imunopositividade em nenhum dos 47 tumores spitzóides avaliáveis. Também não encontramos correlação significativa entre a perda de imunoexpressão de p16 e as categorias diagnósticas. Conclusões. Idade, tamanho e índice mitótico foram critérios diagnósticos significativos para a diferenciação entre MS e as demais categorias. Ulceração, atipia, perda de maturação e presença de células gigantes foram critérios diagnósticos significativos para a diferenciação entre lesões benignas (NS) e lesão não-benignas (AST e MS). A perda de imunoexpressão nuclear de BAP1 foi exclusiva à categoria AST. Não houve imunoexpressão de ALK ou ROS1 xiii em nenhum caso estudado. A avaliação imuno-histoquímica de p16 não permitiu diferenciar tumores benignos (NS) de tumores não-benignos (AST e MS).Dados abertos - Sucupira - Teses e dissertações (2017)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2014/21860-0Universidade Federal de São Paulo (UNIFESP)Landman, Gilles [UNIFESP]http://lattes.cnpq.br/5021275821655717http://lattes.cnpq.br/7040314767086564Universidade Federal de São Paulo (UNIFESP)Cardili, Leonardo [UNIFESP]2019-06-19T14:57:58Z2019-06-19T14:57:58Z2017-10-30info:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/publishedVersion70 f.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5425903http://repositorio.unifesp.br/handle/11600/50477porSão Pauloinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-10T13:35:13Zoai:repositorio.unifesp.br/:11600/50477Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-10T13:35:13Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
Immunoexpression of BAP1, ALK, ROS1 e p16 in spitzoid tumors
title Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
spellingShingle Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
Cardili, Leonardo [UNIFESP]
Spitzoid
BAP1
ROS1
ALK
P16
Nevus, epithelioid and spindle cell
Immunohistochemistry
Nevus, pigmented
Spitzoide
BAP1
ROS1
ALK
P16
Nevo de células epitelioides e fusiformes
Imuno-histoquímica
Nevo pigmentado
title_short Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
title_full Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
title_fullStr Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
title_full_unstemmed Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
title_sort Avaliação da imunoexpressão de BAP1, ALK, ROS1 e P16 em neoplasias melanocíticas spitzoides
author Cardili, Leonardo [UNIFESP]
author_facet Cardili, Leonardo [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Landman, Gilles [UNIFESP]
http://lattes.cnpq.br/5021275821655717
http://lattes.cnpq.br/7040314767086564
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Cardili, Leonardo [UNIFESP]
dc.subject.por.fl_str_mv Spitzoid
BAP1
ROS1
ALK
P16
Nevus, epithelioid and spindle cell
Immunohistochemistry
Nevus, pigmented
Spitzoide
BAP1
ROS1
ALK
P16
Nevo de células epitelioides e fusiformes
Imuno-histoquímica
Nevo pigmentado
topic Spitzoid
BAP1
ROS1
ALK
P16
Nevus, epithelioid and spindle cell
Immunohistochemistry
Nevus, pigmented
Spitzoide
BAP1
ROS1
ALK
P16
Nevo de células epitelioides e fusiformes
Imuno-histoquímica
Nevo pigmentado
description Introduction. Spitzoid tumors represent a heterogeneous group of melanocytic neoplasms. In recent years, several advances in Molecular Biology afforded significant discoveries on the pathogenesis and the biological behavior of these tumors. The BAP1 inactivation, the presence of kinase fusion related-proteins and the role of p16 protein are among the main criteria launched by new classification proposals and represent innovative markers with potential clinical significance. Objetive. To evaluate the immunohistochemical expression of BAP1, ALK, ROS1 and p16 proteins in spitzoid tumors. Methods. Retrospective study based on 47 tissue samples fixed in formalin and embedded in paraffin. This series was composed by the Pathology archives of three cancer reference institutions in the state of São Paulo, Brazil. Clinical-demographic data, histopathological aspects and immunohistochemical results for BAP1, ALK, ROS1 and p16 were studied in this case series composed by 27 Spitz nevus (NS), 15 Atypical Spitzoid Tumors (AST) and 5 Spitzoid Melanomas (MS). Results. Medium age was 21.2 years. Medium histological tumoral width was 5.7 millimeters. We observed statistical significance between diagnostic categories and age, width, mitotic index, ulceration, atypia, loss of maturation and the presence of giant cells. The global frequency of BAP1- inactivated tumors was 4.3% (02/46), both of them AST. The proportional frequency of BAP1-inactivated cases in AST group was 14.2% (02/14). We found no immunostaining for ALK and ROS1 in any out of 47 studied cases. We also did not observe a statistically significant correlation between loss of immunoexpression of p16 and non-benign categories. Conclusions. Age, width and mitotic index were significant diagnostic criteria to differentiate between MS and the remaining categories. Ulceration, atypia, loss of maturation and the presence of giant cells were significant diagnostic criteria to differentiate benign lesions (NS) and non-benignlesions (AST and MS). The loss of nuclear immunoexpression of BAP1 was exclusive to the AST category. We did not observe immunoexpression of ALK or ROS1 in any case. The immunohistochemical evaluation of p16 protein did not allowed differentiation between benign tumors (NS) and non-benign tumors (AST and MS).
publishDate 2017
dc.date.none.fl_str_mv 2017-10-30
2019-06-19T14:57:58Z
2019-06-19T14:57:58Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5425903
http://repositorio.unifesp.br/handle/11600/50477
url https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5425903
http://repositorio.unifesp.br/handle/11600/50477
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 70 f.
application/pdf
dc.coverage.none.fl_str_mv São Paulo
dc.publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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