Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor

Detalhes bibliográficos
Ano de defesa: 2014
Autor(a) principal: Amanda Arantes Perez
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
UFMG
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://hdl.handle.net/1843/BUBD-9ZCN8D
Resumo: Introduction: Ductal carcinoma in situ (DCIS) of the breast is an inherent but not necessarily obligate tendency for progression to invasive breast cancer. The pathogenesis and evolutive aspects of DCIS are still not completely elucidated. A better morphological and molecular evaluation of DCIS would be useful for clinical decision making. The aims of this study were to determine clinical and morphological features, the immunophenotypes of a series of cases of DCIS and to evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions. Methods: This is a retrospective, observational, cross-sectional study. Four hundred and three cases of DCIS, pure or associated with invasive carcinoma, were consecutively identified from the histopathology files of the Breast Pathology Laboratory, School of Medicine, Federal University of Minas Gerais, Brazil, from 2003 to 2008. Immunohistochemistry was performed in 121 highgrade DCIS cases. Estrogen receptor (ER), progesterone receptor (PR), receptor of epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), receptor of epidermal growth factor receptor 1 (EGRF), cyclooxygenase-2 (COX-2), tumor suppressor protein p16 and nuclear antigen Ki67 were assessed. Tumors were placed into five subgroups according to their immunophenotypical profile: luminal A (ER+/HER2-), luminal B (ER+/HER2+), HER2 (ER-/HER2+), basal-like (ER-/HER2-/EGFR+ and/or CK5+), and not classified (all markers negative). Results: The high nuclear grade and the presence of comedonecrosis were identified more frequently in DCIS of younger patients and more often correlated with the solid pattern DCIS (p<0.05). A moderate agreement was observed in the diagnosis of the intraductal proliferative breast lesions, especially atypical ductal hyperplasia, DCIS and DCIS with microinvasion. The most common immunophenotype of pure DCIS was luminal A, followed by HER2 phenotype. The basal-like phenotype was observed only in DCIS associated with invasive carcinoma that had a similar phenotype. No significant difference was identified between pure DCIS and IMC-associated DCIS phenotypes. We observed that p16 expression, isolated or in combination with Ki67 and COX-2, is associated with basal phenotype in high-grade DCIS. Conclusions: A significant discrepancy in the diagnosis of intraductal proliferative breast lesions was observed in our series. The most common type of DCIS was the luminal A. The basal phenotype was less frequent and only seen when associated with basal-type invasive carcinoma. DCIS of high nuclear grade, with comedonecrosis were more often found in younger patients and these characteristics should be considered in the surgical treatment decision. P16 expression, p16+/Ki67+/COX2+ and p16+/Ki67+/COX2- co-expressions showed significant association with basal phenotype and they could be useful to guide more aggressive treatments in patients with high-grade DCIS.
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spelling Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasorCarcinoma ductal in situImunohistoquímicaHistopatologiaMamaCarcinoma ductal de mamaCarcinoma intraductal não infiltranteImuno-histoquímicaCâncerMamaIntroduction: Ductal carcinoma in situ (DCIS) of the breast is an inherent but not necessarily obligate tendency for progression to invasive breast cancer. The pathogenesis and evolutive aspects of DCIS are still not completely elucidated. A better morphological and molecular evaluation of DCIS would be useful for clinical decision making. The aims of this study were to determine clinical and morphological features, the immunophenotypes of a series of cases of DCIS and to evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions. Methods: This is a retrospective, observational, cross-sectional study. Four hundred and three cases of DCIS, pure or associated with invasive carcinoma, were consecutively identified from the histopathology files of the Breast Pathology Laboratory, School of Medicine, Federal University of Minas Gerais, Brazil, from 2003 to 2008. Immunohistochemistry was performed in 121 highgrade DCIS cases. Estrogen receptor (ER), progesterone receptor (PR), receptor of epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), receptor of epidermal growth factor receptor 1 (EGRF), cyclooxygenase-2 (COX-2), tumor suppressor protein p16 and nuclear antigen Ki67 were assessed. Tumors were placed into five subgroups according to their immunophenotypical profile: luminal A (ER+/HER2-), luminal B (ER+/HER2+), HER2 (ER-/HER2+), basal-like (ER-/HER2-/EGFR+ and/or CK5+), and not classified (all markers negative). Results: The high nuclear grade and the presence of comedonecrosis were identified more frequently in DCIS of younger patients and more often correlated with the solid pattern DCIS (p<0.05). A moderate agreement was observed in the diagnosis of the intraductal proliferative breast lesions, especially atypical ductal hyperplasia, DCIS and DCIS with microinvasion. The most common immunophenotype of pure DCIS was luminal A, followed by HER2 phenotype. The basal-like phenotype was observed only in DCIS associated with invasive carcinoma that had a similar phenotype. No significant difference was identified between pure DCIS and IMC-associated DCIS phenotypes. We observed that p16 expression, isolated or in combination with Ki67 and COX-2, is associated with basal phenotype in high-grade DCIS. Conclusions: A significant discrepancy in the diagnosis of intraductal proliferative breast lesions was observed in our series. The most common type of DCIS was the luminal A. The basal phenotype was less frequent and only seen when associated with basal-type invasive carcinoma. DCIS of high nuclear grade, with comedonecrosis were more often found in younger patients and these characteristics should be considered in the surgical treatment decision. P16 expression, p16+/Ki67+/COX2+ and p16+/Ki67+/COX2- co-expressions showed significant association with basal phenotype and they could be useful to guide more aggressive treatments in patients with high-grade DCIS.Introdução: O carcinoma ductal in situ (CDIS) da mama constitui precursor inerente, mas não obrigatório, do carcinoma invasor da mama. O entendimento de sua patogênese e evolução ainda não está completamente elucidado. Aspectos histopatológicos bem avaliados e melhor caracterização molecular do CDIS podem contribuir para condução mais adequada dos casos. Os objetivos deste estudo foram caracterizar aspectos clínicos, histopatológicos e imunofenotípicos de uma série de casos de CDIS e avaliar a concordância interobservador no diagnóstico de lesões mamárias proliferativas intraductais. Métodos: Trata-se de estudo retrospectivo, observacional, do tipo transversal. Foram avaliados, consecutivamente, 403 casos de CDIS, puros ou associados a carcinoma invasor, identificados nos arquivos do Laboratório de Patologia Mamária da Faculdade de Medicina da Universidade Federal de Minas Gerais, de 2003 a 2008. A avaliação imuno-histoquímica foi realizada em 121 casos de CDIS de alto grau, incluindo a pesquisa de receptor de estrógeno (RE), receptor de progesterona (RP), receptor do fator de crescimento epidérmico 2 (HER2), citoqueratina 5, receptor do fator de crescimento epidérmico 1 (EGFR), p16, Ki67 e ciclooxigenase-2 (COX-2). Os tumores foram classificados em cinco subgrupos de acordo com a classificação molecular: luminal A (RE+/HER2-), luminal B (RE+/HER2+), HER2 (RE-/HER2+), basal (RE-/HER2- /EGFR+ e/ou CK5+), não classificável (todos os marcadores negativos). Resultados: O alto grau nuclear e a presença de comedonecrose foram identificados mais frequentemente em pacientes jovens e mais frequentemente correlacionados com o subtipo morfológico sólido do CDIS (p<0,05). As lesões mamárias proliferativas intraductais, em especial a hiperplasia ductal atípica, o CDIS e o CDIS com microinvasão apresentaram concordância moderada na comparação dos diagnósticos histopatológicos. No CDIS puro, o imunofenótipo mais comum foi o luminal A, seguido do subtipo HER2. O imunofenótipo basal foi observado apenas no CDIS associado a carcinoma invasor, que apresentou fenótipo similar. Não houve diferença significativa nos imunofenótipos entre o CDIS puro e associado a carcinoma invasor. A expressão de p16, isolada ou em combinação com Ki67 e COX-2, associou-se ao CDIS de fenótipo basal. Conclusões: Discordância significativa foi observada no diagnóstico das lesões mamárias proliferativas intraductais em nossa série de casos. O imunofenótipo mais frequente entre os CDIS puros e associados a carcinoma invasor foi o luminal A. O tipo basal foi detectado em pequena porcentagem dos casos de CDIS associado a carcinoma invasor com mesmo fenótipo. CDIS com alto grau nuclear e comedonecrose, foi encontrado mais frequentemente em pacientes mais jovens e estas características deveriam ser consideradas na decisão do tratamento cirúrgico. Foi observada correlação positiva entre expressão do p16, COX2, Ki67 e fenótipo basal. Esta co-expressão poderia ser incorporada na rotina para avaliação de CDIS de alto grau com maior potencial evolutivo para carcinoma invasor.Universidade Federal de Minas GeraisUFMGHelenice GobbiCristiana Buzelin NunesDebora BalabramMarcio de Almeida SallesAndre Almeida SchenkaAmanda Arantes Perez2019-08-12T11:52:52Z2019-08-12T11:52:52Z2014-09-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/BUBD-9ZCN8Dinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2019-11-14T20:45:14Zoai:repositorio.ufmg.br:1843/BUBD-9ZCN8DRepositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2019-11-14T20:45:14Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
title Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
spellingShingle Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
Amanda Arantes Perez
Carcinoma ductal in situ
Imunohistoquímica
Histopatologia
Mama
Carcinoma ductal de mama
Carcinoma intraductal não infiltrante
Imuno-histoquímica
Câncer
Mama
title_short Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
title_full Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
title_fullStr Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
title_full_unstemmed Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
title_sort Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor
author Amanda Arantes Perez
author_facet Amanda Arantes Perez
author_role author
dc.contributor.none.fl_str_mv Helenice Gobbi
Cristiana Buzelin Nunes
Debora Balabram
Marcio de Almeida Salles
Andre Almeida Schenka
dc.contributor.author.fl_str_mv Amanda Arantes Perez
dc.subject.por.fl_str_mv Carcinoma ductal in situ
Imunohistoquímica
Histopatologia
Mama
Carcinoma ductal de mama
Carcinoma intraductal não infiltrante
Imuno-histoquímica
Câncer
Mama
topic Carcinoma ductal in situ
Imunohistoquímica
Histopatologia
Mama
Carcinoma ductal de mama
Carcinoma intraductal não infiltrante
Imuno-histoquímica
Câncer
Mama
description Introduction: Ductal carcinoma in situ (DCIS) of the breast is an inherent but not necessarily obligate tendency for progression to invasive breast cancer. The pathogenesis and evolutive aspects of DCIS are still not completely elucidated. A better morphological and molecular evaluation of DCIS would be useful for clinical decision making. The aims of this study were to determine clinical and morphological features, the immunophenotypes of a series of cases of DCIS and to evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions. Methods: This is a retrospective, observational, cross-sectional study. Four hundred and three cases of DCIS, pure or associated with invasive carcinoma, were consecutively identified from the histopathology files of the Breast Pathology Laboratory, School of Medicine, Federal University of Minas Gerais, Brazil, from 2003 to 2008. Immunohistochemistry was performed in 121 highgrade DCIS cases. Estrogen receptor (ER), progesterone receptor (PR), receptor of epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), receptor of epidermal growth factor receptor 1 (EGRF), cyclooxygenase-2 (COX-2), tumor suppressor protein p16 and nuclear antigen Ki67 were assessed. Tumors were placed into five subgroups according to their immunophenotypical profile: luminal A (ER+/HER2-), luminal B (ER+/HER2+), HER2 (ER-/HER2+), basal-like (ER-/HER2-/EGFR+ and/or CK5+), and not classified (all markers negative). Results: The high nuclear grade and the presence of comedonecrosis were identified more frequently in DCIS of younger patients and more often correlated with the solid pattern DCIS (p<0.05). A moderate agreement was observed in the diagnosis of the intraductal proliferative breast lesions, especially atypical ductal hyperplasia, DCIS and DCIS with microinvasion. The most common immunophenotype of pure DCIS was luminal A, followed by HER2 phenotype. The basal-like phenotype was observed only in DCIS associated with invasive carcinoma that had a similar phenotype. No significant difference was identified between pure DCIS and IMC-associated DCIS phenotypes. We observed that p16 expression, isolated or in combination with Ki67 and COX-2, is associated with basal phenotype in high-grade DCIS. Conclusions: A significant discrepancy in the diagnosis of intraductal proliferative breast lesions was observed in our series. The most common type of DCIS was the luminal A. The basal phenotype was less frequent and only seen when associated with basal-type invasive carcinoma. DCIS of high nuclear grade, with comedonecrosis were more often found in younger patients and these characteristics should be considered in the surgical treatment decision. P16 expression, p16+/Ki67+/COX2+ and p16+/Ki67+/COX2- co-expressions showed significant association with basal phenotype and they could be useful to guide more aggressive treatments in patients with high-grade DCIS.
publishDate 2014
dc.date.none.fl_str_mv 2014-09-25
2019-08-12T11:52:52Z
2019-08-12T11:52:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/BUBD-9ZCN8D
url http://hdl.handle.net/1843/BUBD-9ZCN8D
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 application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
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institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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