Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário

Detalhes bibliográficos
Autor(a) principal: Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]
Data de Publicação: 2016
Tipo de documento: Tese
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=4156285
http://repositorio.unifesp.br/handle/11600/46995
Resumo: Research bases: Breast cancer is the most frequent malignancy in the world, and many of these women develop distant metastases, most often to the bones, lymph nodes, lung, brain and liver. Metastases to the gastrointestinal tract are rare, but when present the stomach is the most common site. The differential diagnosis between gastric metastasis of mammary origin and primary gastric adenocarcinoma is difficult, and the radiological and endoscopic findings are similar and the morphological characteristics often do not allow the diagnosis of the cancer origin, hindering thus the proper treatment. Objective: The motivation and the goal of this research were to search the characterization of the molecular expression profile of markers in the primary site of breast carcinoma in gastric metastasis site and the second synchronous gastric primary or metachronous, in order to identify possible markers that facilitate the diagnosis of gastric metastases of mammary origin. Methods: The proposed research design was retrospective and controlled nature, making up three focus groups with 42 patients each, for a total of 126 patients; The Test group included patients with breast cancer who developed primary gastric adenocarcinoma (n=17) and metastatic mammary carcinoma in the stomach (n=25) diagnosed prior to treatment; the Control group I included patients diagnosed with primary breast carcinoma, without other associated lesions and the Control group II included patients with primary gastric adenocarcinoma, also without other associated lesions. The markers selected for analysis were: estrogen receptor (ER), progesterone receptor (PR), gross cystic disease fluid protein-15 (GCDFP-15) and hepatocyte nuclear factor 4-alpha (HNF4A), which were examined in tumor samples in 126 paraffin blocks, the Test and Controls groups I and II. The sensitivities, specific, accurate, prevalence, predictive values were calculated, estimating the test group the confidence intervals of values. Results: The tumor marker ER showed positive immunoreactivity in 12/25 patients (48.0%) with metastatic breast cancer in the stomach, sensitivity 48.0%, specificity of 100.0% and accuracy of 69.0%, with p<0.001; tumor marker PR showed positive immunoreactivity in 6/25 patients (24.0%) with metastatic breast cancer in the stomach, 24.0% sensitivity, specificity 100.0% and accuracy of 54.8%, with p<0.001; the GCDFP-15 marker showed positive immunoreactivity in 9/25 patients (36.0%) with metastatic breast cancer in the stomach, sensitivity 36.0%, specificity of 100.0% and accuracy of 61.9%, with p<0.001; tumor marker HNF4A showed positive immunoreactivity in 17/17 patients (100.0%) with primary gastric adenocarcinoma and negative in 1 patient with metastatic breast cancer in the stomach, 100.0% sensitivity, high specificity of 96.0% and accuracy of 97.6% with p value <0.001. Conclusion: Based on the results obtained in this research we can conclude that HNF4A, ER, PR and GCDFP-15 markers are effective in the differential diagnosis of primary gastric cancer and gastric metastasis of mammary origin. The marker HNF4A, in particular, can be regarded as highly significant to the exclusion of metastatic mammary carcinoma in the stomach, and thus can confer high power reliability in distinguishing these lesions.
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spelling Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primárioComparative and controlled analysis between immunohistochemical profiles of breast carcinoma, gastric metastasis of mammary origin and primary gastric adenocarcinomaHnf4aImmunohistochemistryBiomarkerGastric cancerGastric metastasesHnf4aImuno-histoquímicaBiomarcadorCancer gástricoMetastase gástricaResearch bases: Breast cancer is the most frequent malignancy in the world, and many of these women develop distant metastases, most often to the bones, lymph nodes, lung, brain and liver. Metastases to the gastrointestinal tract are rare, but when present the stomach is the most common site. The differential diagnosis between gastric metastasis of mammary origin and primary gastric adenocarcinoma is difficult, and the radiological and endoscopic findings are similar and the morphological characteristics often do not allow the diagnosis of the cancer origin, hindering thus the proper treatment. Objective: The motivation and the goal of this research were to search the characterization of the molecular expression profile of markers in the primary site of breast carcinoma in gastric metastasis site and the second synchronous gastric primary or metachronous, in order to identify possible markers that facilitate the diagnosis of gastric metastases of mammary origin. Methods: The proposed research design was retrospective and controlled nature, making up three focus groups with 42 patients each, for a total of 126 patients; The Test group included patients with breast cancer who developed primary gastric adenocarcinoma (n=17) and metastatic mammary carcinoma in the stomach (n=25) diagnosed prior to treatment; the Control group I included patients diagnosed with primary breast carcinoma, without other associated lesions and the Control group II included patients with primary gastric adenocarcinoma, also without other associated lesions. The markers selected for analysis were: estrogen receptor (ER), progesterone receptor (PR), gross cystic disease fluid protein-15 (GCDFP-15) and hepatocyte nuclear factor 4-alpha (HNF4A), which were examined in tumor samples in 126 paraffin blocks, the Test and Controls groups I and II. The sensitivities, specific, accurate, prevalence, predictive values were calculated, estimating the test group the confidence intervals of values. Results: The tumor marker ER showed positive immunoreactivity in 12/25 patients (48.0%) with metastatic breast cancer in the stomach, sensitivity 48.0%, specificity of 100.0% and accuracy of 69.0%, with p<0.001; tumor marker PR showed positive immunoreactivity in 6/25 patients (24.0%) with metastatic breast cancer in the stomach, 24.0% sensitivity, specificity 100.0% and accuracy of 54.8%, with p<0.001; the GCDFP-15 marker showed positive immunoreactivity in 9/25 patients (36.0%) with metastatic breast cancer in the stomach, sensitivity 36.0%, specificity of 100.0% and accuracy of 61.9%, with p<0.001; tumor marker HNF4A showed positive immunoreactivity in 17/17 patients (100.0%) with primary gastric adenocarcinoma and negative in 1 patient with metastatic breast cancer in the stomach, 100.0% sensitivity, high specificity of 96.0% and accuracy of 97.6% with p value <0.001. Conclusion: Based on the results obtained in this research we can conclude that HNF4A, ER, PR and GCDFP-15 markers are effective in the differential diagnosis of primary gastric cancer and gastric metastasis of mammary origin. The marker HNF4A, in particular, can be regarded as highly significant to the exclusion of metastatic mammary carcinoma in the stomach, and thus can confer high power reliability in distinguishing these lesions.Bases da investigação: o câncer de mama é a neoplasia maligna mais incidente em todo o mundo e muitas dessas mulheres desenvolvem metástases distantes, mais frequentemente para os ossos, linfonodos, pulmão, cérebro e fígado. Metástases para o trato gastrointestinal são raras, mas quando presentes o estômago é um dos locais mais comuns. O diagnóstico diferencial entre a metástase gástrica de origem mamária e o adenocarcinoma gástrico primário é difícil, os achados radiológicos e endoscópicos são semelhantes e as características morfológicas muitas vezes não permitem o diagnóstico da origem da neoplasia, dificultando a conduta terapêutica adequada. Objetivo: a motivação e o objetivo desta investigação foram a busca da caracterização do perfil de expressão de marcadores moleculares no carcinoma mamário, na metástase gástrica e no segundo primário gástrico sincrônico ou metacrônico, de forma a identificar possíveis marcadores que facilitem o diagnóstico da metástase gástrica de origem mamária. Métodos: o desenho de pesquisa proposto foi de natureza retrospectiva e controlada, compondo-se três grupos de análise com 42 pacientes cada, em um total de 126 pacientes; o grupo Teste incluiu pacientes com carcinoma mamário e que desenvolveram adenocarcinoma gástrico primário (n=17) ou carcinoma mamário metastático no estômago (n=25), diagnosticados previamente ao tratamento; o grupo Controle I incluiu pacientes com diagnóstico de carcinoma mamário primário, sem outras lesões associadas e o grupo Controle II incluiu pacientes com diagnóstico de adenocarcinoma gástrico primário, também sem outras lesões associadas. Os marcadores selecionados para análise incluíram: o receptor de estrogênio (RE), o receptor de progesterona (RP), a gross cystic disease fluid protein-15 (GCDFP-15) e o hepatocyte nuclear factor 4-alpha (HNF4A), que foram analisados nas amostras do carcinoma em 126 blocos de parafina, nos grupos Teste e Controles I e II. Foram calculadas as sensibilidades, especificidades, acurácia, prevalência, valores preditivos, estimando-se no grupo Teste os intervalos de confiança dos valores obtidos. Resultados: o marcador tumoral RE apresentou imunoexpressão positiva em 12/25 pacientes (48,0%) com carcinoma mamário metastático no estômago, sensibilidade de 48,0%, especificidade de 100,0% e acurácia de 69,0%, com valor de p<0,001; o marcador tumoral RP apresentou imunoexpressão positiva em 6/25 pacientes (24,0%) com carcinoma mamário metastático no estômago, sensibilidade de 24,0%, especificidade de 100,0% e acurácia de 54,8%, com valor de p<0,001; o marcador GCDFP-15 apresentou imunoexpressão positiva em 9/25 pacientes (36,0%) com carcinoma mamário metastático no estômago, sensibilidade de 36,0%, especificidade de 100,0% e acurácia de 61,9%, com valor de p<0,001; o marcador tumoral HNF4A apresentou imunoexpressão positiva em 17/17 pacientes (100,0%) com adenocarcinoma gástrico primário, e positivo em 1 paciente com carcinoma mamário metastático no estômago, sensibilidade de 100,0%, alta especificidade de 96,0% e acurácia de 97,6%, com valor de p<0,001. Conclusão: com base nos resultados obtidos nesta investigação podemos concluir que os marcadores HNF4A, RE, RP e GCDFP-15 são efetivos no diagnóstico diferencial entre câncer gástrico primário e metástase gástrica de origem mamária. O marcador HNF4A, em particular, pode ser considerado como altamente significante para a exclusão de carcinoma mamário metastático no estômago, e que pode conferir desta forma alto poder de confiabilidade na distinção destas lesões.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016)Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP)Matos, Delcio [UNIFESP]http://lattes.cnpq.br/8504991156956921http://lattes.cnpq.br/8810661976171757Universidade Federal de São Paulo (UNIFESP)Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]2018-07-27T15:51:12Z2018-07-27T15:51:12Z2016-11-29info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion72 f.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4156285JUCA, Patricia Chaves de Freitas Campos. Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário. 2016. 72 f. Tese (Doutorado em Ciência Cirúrgica Interdisciplinar) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2016.PATRÍCIA CHAVES DE FREITAS CAMPOS JUCÁ - PDF A.pdfhttp://repositorio.unifesp.br/handle/11600/46995porSão Pauloinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-01T12:50:10Zoai:repositorio.unifesp.br/:11600/46995Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-01T12:50:10Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
Comparative and controlled analysis between immunohistochemical profiles of breast carcinoma, gastric metastasis of mammary origin and primary gastric adenocarcinoma
title Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
spellingShingle Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]
Hnf4a
Immunohistochemistry
Biomarker
Gastric cancer
Gastric metastases
Hnf4a
Imuno-histoquímica
Biomarcador
Cancer gástrico
Metastase gástrica
title_short Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
title_full Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
title_fullStr Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
title_full_unstemmed Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
title_sort Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário
author Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]
author_facet Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Matos, Delcio [UNIFESP]
http://lattes.cnpq.br/8504991156956921
http://lattes.cnpq.br/8810661976171757
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Jucá, Patrícia Chaves de Freitas Campos [UNIFESP]
dc.subject.por.fl_str_mv Hnf4a
Immunohistochemistry
Biomarker
Gastric cancer
Gastric metastases
Hnf4a
Imuno-histoquímica
Biomarcador
Cancer gástrico
Metastase gástrica
topic Hnf4a
Immunohistochemistry
Biomarker
Gastric cancer
Gastric metastases
Hnf4a
Imuno-histoquímica
Biomarcador
Cancer gástrico
Metastase gástrica
description Research bases: Breast cancer is the most frequent malignancy in the world, and many of these women develop distant metastases, most often to the bones, lymph nodes, lung, brain and liver. Metastases to the gastrointestinal tract are rare, but when present the stomach is the most common site. The differential diagnosis between gastric metastasis of mammary origin and primary gastric adenocarcinoma is difficult, and the radiological and endoscopic findings are similar and the morphological characteristics often do not allow the diagnosis of the cancer origin, hindering thus the proper treatment. Objective: The motivation and the goal of this research were to search the characterization of the molecular expression profile of markers in the primary site of breast carcinoma in gastric metastasis site and the second synchronous gastric primary or metachronous, in order to identify possible markers that facilitate the diagnosis of gastric metastases of mammary origin. Methods: The proposed research design was retrospective and controlled nature, making up three focus groups with 42 patients each, for a total of 126 patients; The Test group included patients with breast cancer who developed primary gastric adenocarcinoma (n=17) and metastatic mammary carcinoma in the stomach (n=25) diagnosed prior to treatment; the Control group I included patients diagnosed with primary breast carcinoma, without other associated lesions and the Control group II included patients with primary gastric adenocarcinoma, also without other associated lesions. The markers selected for analysis were: estrogen receptor (ER), progesterone receptor (PR), gross cystic disease fluid protein-15 (GCDFP-15) and hepatocyte nuclear factor 4-alpha (HNF4A), which were examined in tumor samples in 126 paraffin blocks, the Test and Controls groups I and II. The sensitivities, specific, accurate, prevalence, predictive values were calculated, estimating the test group the confidence intervals of values. Results: The tumor marker ER showed positive immunoreactivity in 12/25 patients (48.0%) with metastatic breast cancer in the stomach, sensitivity 48.0%, specificity of 100.0% and accuracy of 69.0%, with p<0.001; tumor marker PR showed positive immunoreactivity in 6/25 patients (24.0%) with metastatic breast cancer in the stomach, 24.0% sensitivity, specificity 100.0% and accuracy of 54.8%, with p<0.001; the GCDFP-15 marker showed positive immunoreactivity in 9/25 patients (36.0%) with metastatic breast cancer in the stomach, sensitivity 36.0%, specificity of 100.0% and accuracy of 61.9%, with p<0.001; tumor marker HNF4A showed positive immunoreactivity in 17/17 patients (100.0%) with primary gastric adenocarcinoma and negative in 1 patient with metastatic breast cancer in the stomach, 100.0% sensitivity, high specificity of 96.0% and accuracy of 97.6% with p value <0.001. Conclusion: Based on the results obtained in this research we can conclude that HNF4A, ER, PR and GCDFP-15 markers are effective in the differential diagnosis of primary gastric cancer and gastric metastasis of mammary origin. The marker HNF4A, in particular, can be regarded as highly significant to the exclusion of metastatic mammary carcinoma in the stomach, and thus can confer high power reliability in distinguishing these lesions.
publishDate 2016
dc.date.none.fl_str_mv 2016-11-29
2018-07-27T15:51:12Z
2018-07-27T15:51:12Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format doctoralThesis
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=4156285
JUCA, Patricia Chaves de Freitas Campos. Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário. 2016. 72 f. Tese (Doutorado em Ciência Cirúrgica Interdisciplinar) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2016.
PATRÍCIA CHAVES DE FREITAS CAMPOS JUCÁ - PDF A.pdf
http://repositorio.unifesp.br/handle/11600/46995
url https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4156285
http://repositorio.unifesp.br/handle/11600/46995
identifier_str_mv JUCA, Patricia Chaves de Freitas Campos. Análise comparativa e controlada entre os perfis moleculares imuno-histoquímicos do carcinoma mamário, da metástase gástrica de origem mamária e do adenocarcinoma gástrico primário. 2016. 72 f. Tese (Doutorado em Ciência Cirúrgica Interdisciplinar) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2016.
PATRÍCIA CHAVES DE FREITAS CAMPOS JUCÁ - PDF A.pdf
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 72 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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