Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida

Detalhes bibliográficos
Autor(a) principal: Soares, Nicolle Pereira
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/28770
http://dx.doi.org/10.14393/ufu.te.2019.1253
Resumo: Neoplasias are the most common affections in dogs, and the spontaneous mammary tumors are the most frequent in female bitches. More than 50% of the cases are malignant and it represent a heterogeneity disease group with variable morphology and biological behavior. Molecular expression of estrogen receptors (ER) and progesterone receptors (PR) are considered prognostic factors, and ER expression is essential for determination of molecular classification. Another molecular marker frequently evaluated in human breast cancer is type 2 human epidermal growth factor (HER2). 84 bitches were included in this study. The radiographic and ultrasound examination were performed in orden to verify metastases in lung and nodal metastases. The surgical excision was a treatment for the mammary tumor (total or bilateral unilateral mastectomy). Samples of mammary neoplasms were evaluated for histological type and the expression of ER, PR e HER2 by immunohistochemistry. Evaluation of total overall survival (OS), disease-free interval (DFS) and time to tumor development in remaining breast (TDTMR) was performed. ST was defined as time after mastectomy up to the date of death; the DFS was the time after mastectomy until the development of recurrence or metastasis, and the TDTMR was determined as the time after mastectomy until the appearance of tumor in the remaining mammary gland. In the bitch, it is often expressed in malignant mammary carcinoma and correlates with nuclear pleomorphism, high histological grade and mitotic index, as well as lower survival. Absence of ER, PR and HER2 expression characterizes the triple negative phenotype. In women, this phenotype is related to aggressive tumor histology, poor prognosis, presence of metastases and recurrences. In bitch, they also present aggressive behavior, poor prognosis and reduction of survival. The objective of this study was to verify the expression of ER and the frequency of triple negative phenotype in canine mammary carcinomas (CMC) and correlate them with clinicopathological characteristics, overall survival (OS), disease-free interval and tumor development time in the breast remaining in bitches. In this study, the expression of estrogen was identified in 30.95% of canine mammary carcinomas, old-aged bitches, complex histological type grade II. Age was identified as a prognostic factor in canine mammary tumors and neoplasms of lower histological grade expressed more RE. The isolated evaluation of this molecular marker was not a good prognostic factor when considering total survival (483.42 ± 319.17 days) disease-free time (234.45 ± 241.05 days) and the time of tumor development in remaining mammary gland (279.68 ± 317.75 days). Furthermore, 21.43% of CMC were identified as a triple negative phenotype. None of the clinicopathological parameters evaluated (type and histological grade, clinical stages, stromal invasiveness, age, size and tumor location) differed significantly between the two CMC groups (triple negative and non triple negative), except for castration. In addition, we observed a correlation of this variable in the multivariate analysis with ST (471.42 ± 353.45 days). The behavior of the triple negative CMC seems to be less aggressive than in woman. The use of other molecular markers (Ki67, P53, P-caderina) must be used to distinguish the molecular subgroups in triple negative phenotype, and lead to the identification of more or less aggressive triple negative phenotypes. As similar CMC in general, castration may influence the occurrence of CMC triple negative.
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spelling Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevidaMolecular immunophenotype of canine mammary carcinomas and the relationship with prognostic factors and survivalCastraçãoCastrationReceptores de estrógenoEstrogen receptorsReceptores de progesteronaProgesterone receptorsTumores mamários caninosMammary gland tumorsHER2CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA::PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMALNeoplasias are the most common affections in dogs, and the spontaneous mammary tumors are the most frequent in female bitches. More than 50% of the cases are malignant and it represent a heterogeneity disease group with variable morphology and biological behavior. Molecular expression of estrogen receptors (ER) and progesterone receptors (PR) are considered prognostic factors, and ER expression is essential for determination of molecular classification. Another molecular marker frequently evaluated in human breast cancer is type 2 human epidermal growth factor (HER2). 84 bitches were included in this study. The radiographic and ultrasound examination were performed in orden to verify metastases in lung and nodal metastases. The surgical excision was a treatment for the mammary tumor (total or bilateral unilateral mastectomy). Samples of mammary neoplasms were evaluated for histological type and the expression of ER, PR e HER2 by immunohistochemistry. Evaluation of total overall survival (OS), disease-free interval (DFS) and time to tumor development in remaining breast (TDTMR) was performed. ST was defined as time after mastectomy up to the date of death; the DFS was the time after mastectomy until the development of recurrence or metastasis, and the TDTMR was determined as the time after mastectomy until the appearance of tumor in the remaining mammary gland. In the bitch, it is often expressed in malignant mammary carcinoma and correlates with nuclear pleomorphism, high histological grade and mitotic index, as well as lower survival. Absence of ER, PR and HER2 expression characterizes the triple negative phenotype. In women, this phenotype is related to aggressive tumor histology, poor prognosis, presence of metastases and recurrences. In bitch, they also present aggressive behavior, poor prognosis and reduction of survival. The objective of this study was to verify the expression of ER and the frequency of triple negative phenotype in canine mammary carcinomas (CMC) and correlate them with clinicopathological characteristics, overall survival (OS), disease-free interval and tumor development time in the breast remaining in bitches. In this study, the expression of estrogen was identified in 30.95% of canine mammary carcinomas, old-aged bitches, complex histological type grade II. Age was identified as a prognostic factor in canine mammary tumors and neoplasms of lower histological grade expressed more RE. The isolated evaluation of this molecular marker was not a good prognostic factor when considering total survival (483.42 ± 319.17 days) disease-free time (234.45 ± 241.05 days) and the time of tumor development in remaining mammary gland (279.68 ± 317.75 days). Furthermore, 21.43% of CMC were identified as a triple negative phenotype. None of the clinicopathological parameters evaluated (type and histological grade, clinical stages, stromal invasiveness, age, size and tumor location) differed significantly between the two CMC groups (triple negative and non triple negative), except for castration. In addition, we observed a correlation of this variable in the multivariate analysis with ST (471.42 ± 353.45 days). The behavior of the triple negative CMC seems to be less aggressive than in woman. The use of other molecular markers (Ki67, P53, P-caderina) must be used to distinguish the molecular subgroups in triple negative phenotype, and lead to the identification of more or less aggressive triple negative phenotypes. As similar CMC in general, castration may influence the occurrence of CMC triple negative.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFAPEMIG - Fundação de Amparo a Pesquisa do Estado de Minas GeraisTese (Doutorado)As neoplasias estão entre as afecções mais comuns em cães, sendo que tumores mamários espontâneos são os mais frequentes em cadelas fêmeas. Mais de 50% dos casos são malignos e representam um grupo de grande heterogeneidade em termos de morfologia e comportamento biológico. A expressão molecular de receptores de estrógeno (RE) e receptores de progesterona (RP) são considerados fatores de prognóstico, sendo a expressão de RE essencial para determinação da caracterização molecular. Outro marcador molecular frequentemente avaliado em oncologia humana é o fator de crescimento epidérmico humano tipo 2 (HER2), na cadela, é frequentemente expresso em tumores mamários malignos e correlaciona-se com pleomorfismo nuclear, alto grau histológico e índice mitótico, além de menor sobrevida. A ausência de expressão de RE, RP e HER2 caracteriza o fenótipo triplo negativo. Na mulher este fenótipo está relacionado a histologia tumoral agressiva, prognóstico ruim, presença de metástases e recidivas. Na cadela também apresentam comportamento agressivo, prognóstico desfavorável e redução de sobrevida. Objetivou-se neste trabalho verificar a expressão de RE e a frequência do fenótipo triplo negativo em carcinomas mamários caninos (CMC) e correlacioná-las com características clinicopatológicas, sobrevida global (SG), intervalo livre de doença e tempo de desenvolvimento de tumor em mama remanescente em cadelas. Foram incluídas neste estudo 84 cadelas. Elas foram submetidas a exame radiográfico e de ultrassonografia, para avaliação de metástases pulmonares e a distância, e que realizaram exérese cirúrgica como tratamento para o tumor de mama (mastectomia unilateral total ou bilateral total). As amostras de neoplasias mamárias foram avaliadas quanto ao tipo e grau histológico, invasividade estromal, e a expressão de RE, RP e HER2 por meio de imunohistoquímica. Neste estudo, a expressão de estrógeno foi identificada em 30,95% de carcinomas mamários caninos, de cadelas idosas, tipo histológico complexo grau II. A idade foi identificada como fator de prognóstico nos tumores mamários de cadelas e neoplasias de menor grau histológico expressam mais RE. A avaliação isolada deste marcador molecular não foi um bom fator de prognóstico quando se considera sobrevida global (483,42 ±319,17 dias) tempo livre de doença (234,45 ±241,05 dias) e o tempo de desenvolvimento de tumor em mama remanescente (279,68 ±317,75 dias). Ainda, 21,43% dos CMC foram identificados como fenótipo triplo negativo. Nenhum dos parâmetros clinicopatológicos avaliados (tipo e grau histológico, estadios clínicos, invasividade estromal, idade, tamanho e localização tumoral) diferiram significativamente entre os dois grupos de CMC (triplo negativos e não triplo negativos), exceto a castração. Além disso, observou-se correlação desta variável, na análise multivariada, com a SG (471,42±353,45 dias). O comportamento dos CMC triplo negativo parece ser menos agressivo quando comparado com o da mulher. A utilização de outros marcadores moleculares, como Ki-67, P53, P-caderima, podem auxiliar na diferenciação de subgrupos moleculares dentro do fenótipo triplo negativo e levar à identificação de fenótipos triplo negativos mais ou menos agressivos. Assim como ocorre com CMC em geral, a castração pode influenciar na ocorrência de CMC triplo negativo.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Ciências VeterináriasMedeiros-Ronchi, Alessandra Aparecidahttp://lattes.cnpq.br/6877724175343385Gobbi, Helenicehttp://lattes.cnpq.br/6734743384464724Magalhães, Geórgia Modéhttp://lattes.cnpq.br/7952251706145257João, Carolina Franchhttp://lattes.cnpq.br/1743045211710725Szabó, Matias Pablo Juanhttp://lattes.cnpq.br/7340697197436800Soares, Nicolle Pereira2020-02-18T19:56:08Z2020-02-18T19:56:08Z2019-05-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfSOARES, Nicolle Pereira. Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida. 2019. 88 f. Tese (Doutorado em Ciências Veterinárias) - Universidade Federal de Uberlândia, Uberlândia, 2019. DOI http://dx.doi.org/10.14393/ufu.te.2019.1253https://repositorio.ufu.br/handle/123456789/28770http://dx.doi.org/10.14393/ufu.te.2019.1253porhttp://creativecommons.org/licenses/by-nc-sa/3.0/us/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2021-12-01T15:00:42Zoai:repositorio.ufu.br:123456789/28770Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2021-12-01T15:00:42Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
Molecular immunophenotype of canine mammary carcinomas and the relationship with prognostic factors and survival
title Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
spellingShingle Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
Soares, Nicolle Pereira
Castração
Castration
Receptores de estrógeno
Estrogen receptors
Receptores de progesterona
Progesterone receptors
Tumores mamários caninos
Mammary gland tumors
HER2
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA::PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMAL
title_short Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
title_full Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
title_fullStr Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
title_full_unstemmed Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
title_sort Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida
author Soares, Nicolle Pereira
author_facet Soares, Nicolle Pereira
author_role author
dc.contributor.none.fl_str_mv Medeiros-Ronchi, Alessandra Aparecida
http://lattes.cnpq.br/6877724175343385
Gobbi, Helenice
http://lattes.cnpq.br/6734743384464724
Magalhães, Geórgia Modé
http://lattes.cnpq.br/7952251706145257
João, Carolina Franch
http://lattes.cnpq.br/1743045211710725
Szabó, Matias Pablo Juan
http://lattes.cnpq.br/7340697197436800
dc.contributor.author.fl_str_mv Soares, Nicolle Pereira
dc.subject.por.fl_str_mv Castração
Castration
Receptores de estrógeno
Estrogen receptors
Receptores de progesterona
Progesterone receptors
Tumores mamários caninos
Mammary gland tumors
HER2
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA::PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMAL
topic Castração
Castration
Receptores de estrógeno
Estrogen receptors
Receptores de progesterona
Progesterone receptors
Tumores mamários caninos
Mammary gland tumors
HER2
CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA::PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMAL
description Neoplasias are the most common affections in dogs, and the spontaneous mammary tumors are the most frequent in female bitches. More than 50% of the cases are malignant and it represent a heterogeneity disease group with variable morphology and biological behavior. Molecular expression of estrogen receptors (ER) and progesterone receptors (PR) are considered prognostic factors, and ER expression is essential for determination of molecular classification. Another molecular marker frequently evaluated in human breast cancer is type 2 human epidermal growth factor (HER2). 84 bitches were included in this study. The radiographic and ultrasound examination were performed in orden to verify metastases in lung and nodal metastases. The surgical excision was a treatment for the mammary tumor (total or bilateral unilateral mastectomy). Samples of mammary neoplasms were evaluated for histological type and the expression of ER, PR e HER2 by immunohistochemistry. Evaluation of total overall survival (OS), disease-free interval (DFS) and time to tumor development in remaining breast (TDTMR) was performed. ST was defined as time after mastectomy up to the date of death; the DFS was the time after mastectomy until the development of recurrence or metastasis, and the TDTMR was determined as the time after mastectomy until the appearance of tumor in the remaining mammary gland. In the bitch, it is often expressed in malignant mammary carcinoma and correlates with nuclear pleomorphism, high histological grade and mitotic index, as well as lower survival. Absence of ER, PR and HER2 expression characterizes the triple negative phenotype. In women, this phenotype is related to aggressive tumor histology, poor prognosis, presence of metastases and recurrences. In bitch, they also present aggressive behavior, poor prognosis and reduction of survival. The objective of this study was to verify the expression of ER and the frequency of triple negative phenotype in canine mammary carcinomas (CMC) and correlate them with clinicopathological characteristics, overall survival (OS), disease-free interval and tumor development time in the breast remaining in bitches. In this study, the expression of estrogen was identified in 30.95% of canine mammary carcinomas, old-aged bitches, complex histological type grade II. Age was identified as a prognostic factor in canine mammary tumors and neoplasms of lower histological grade expressed more RE. The isolated evaluation of this molecular marker was not a good prognostic factor when considering total survival (483.42 ± 319.17 days) disease-free time (234.45 ± 241.05 days) and the time of tumor development in remaining mammary gland (279.68 ± 317.75 days). Furthermore, 21.43% of CMC were identified as a triple negative phenotype. None of the clinicopathological parameters evaluated (type and histological grade, clinical stages, stromal invasiveness, age, size and tumor location) differed significantly between the two CMC groups (triple negative and non triple negative), except for castration. In addition, we observed a correlation of this variable in the multivariate analysis with ST (471.42 ± 353.45 days). The behavior of the triple negative CMC seems to be less aggressive than in woman. The use of other molecular markers (Ki67, P53, P-caderina) must be used to distinguish the molecular subgroups in triple negative phenotype, and lead to the identification of more or less aggressive triple negative phenotypes. As similar CMC in general, castration may influence the occurrence of CMC triple negative.
publishDate 2019
dc.date.none.fl_str_mv 2019-05-09
2020-02-18T19:56:08Z
2020-02-18T19:56:08Z
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 SOARES, Nicolle Pereira. Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida. 2019. 88 f. Tese (Doutorado em Ciências Veterinárias) - Universidade Federal de Uberlândia, Uberlândia, 2019. DOI http://dx.doi.org/10.14393/ufu.te.2019.1253
https://repositorio.ufu.br/handle/123456789/28770
http://dx.doi.org/10.14393/ufu.te.2019.1253
identifier_str_mv SOARES, Nicolle Pereira. Imunofenótipo molecular de carcinomas mamários caninos e sua relação com fatores de prognóstico e sobrevida. 2019. 88 f. Tese (Doutorado em Ciências Veterinárias) - Universidade Federal de Uberlândia, Uberlândia, 2019. DOI http://dx.doi.org/10.14393/ufu.te.2019.1253
url https://repositorio.ufu.br/handle/123456789/28770
http://dx.doi.org/10.14393/ufu.te.2019.1253
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-sa/3.0/us/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/3.0/us/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Ciências Veterinárias
publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Ciências Veterinárias
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
instacron:UFU
instname_str Universidade Federal de Uberlândia (UFU)
instacron_str UFU
institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
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