Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes

Detalhes bibliográficos
Ano de defesa: 2024
Autor(a) principal: Oliveira, Dênia Reis de Paula [UNESP]
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Estadual Paulista (Unesp)
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: https://hdl.handle.net/11449/255476
Resumo: Objective: To evaluate the association between imaging characteristics of breast carcinomas (by the BI-RADS ® [5th Edition]) mammographic and ultrasonographic descriptors) and tumor histological characteristics, with the molecular subtypes approximated by immunohistochemistry (IHC) and with the overall survival (OS), Cancer Specific Survival (CCS) and Disease-Free Survival (DFS) of affected patients. Methods: This is a single-center, retrospective cohort. This study included patients diagnosed with invasive breast cancer between 2012 and 2015, age ≥ 18 years, in stages I, II and III. The included patients underwent diagnosis and follow-up at the Hospital das Clínicas de Botucatu, with mammography, ultrasound and histopathological data archived in the Hospital's medical records. Clinical, imaging and anatomopathological data were collected. The association between imaging descriptors, biomarkers and histological subtypes was analyzed. To study the association of variables and compare proportions, the chi-square test was used. The primary outcome was OS and secondary outcomes were DFS and CSS. Kaplan-Meier curve and Cox regression model were used to evaluate the association between imaging descriptors and OS, DFS and CSS. Differences in survival rates were assessed using hazard ratio (HR). In all tests, a significance level of 5% or the corresponding p-value was adopted. Results: The study included 260 women with a mean age of 56.3 ± 12.4 years at diagnosis, mean tumor size of de 2.6cm ±1,63 cm and follow up period of 114 months. The main mammography findings were: nodular lesions were associated with ER -, HER-2 negative and Ki-67 ≥ 20%. The irregular shape was associated with less aggressive lesions (RE+, RP+ and Ki-67 <20%). Round lesions were frequently related to Ki-67≥20%. Regarding the margin, while the circumscribed, microlobulated and obscured margins were linked to hormone receptor negativity, the spiculated margin was more frequent in ER and PR positive carcinomas. HER-2 suppression was more common in indistinct and microlobulated tumors, in the presence of asymmetries and suspicious microcalcifications. Finally, the suspicious axilla was more closely related to ER-, RP-, HER-2 + and high Ki-67. Regarding molecular subtypes, non-mass lesions and nodules with indistinct or microlobulated margins were associated with the hybrid subtype, while triple-negative (TN) tumors were mostly nodular, with an oval or round shape, with a circumscribed or obscured margin. The suspicious axilla in MMG was inversely associated with the Luminal B subtype and directly associated with pure HER-2. Also, in the HER-2 subtype, the presence of suspicious microcalcifications was statistically significant. Regarding ultrasound findings: of the microlobulated tumors, the majority were grade 3. Undifferentiated tumors were also more frequent with heterogeneous echogenicity, parallel orientation, posterior acoustic reinforcement and suspicious axillary lymph nodes. Grade 1 tumors were associated with hypoechogenic, non-parallel lesions, with shadow or combined pattern, with echogenic halo and negative axilla. Grade 2 carcinomas only showed an association with no subsequent effect. ER and PR positive tumors were irregular, with an angled, spiculated or indistinct margin, hypoechoic, non-parallel, with an echogenic halo, with shadow or absence of posterior acoustic effect and with a negative axilla. Negative ER and PR, in turn, presented an oval or round shape, microlobulated margins, heterogeneous echotexture, reinforcement, suspicious axilla on US and an inverse association with the presence of the halo. The mixed effect, despite being related to RE+, was mostly RP-. The PR was also negative in tumors that showed flow on Doppler. Regarding tumors with HER-2 overexpression, the minority had posterior shadowing. As for Ki-67, high rates were associated with oval or round lesions, with microlobulated or angled margins, heterogeneous, reinforcement, Doppler flow and suspicious axilla. Regarding subtypes, Luminal A were irregular, hypoechogenic, non-parallel, without Doppler flow or suspicious microcalcification, with posterior acoustic shadow and negative axilla. Luminal B, in turn, was associated with non-parallel orientation. HER-2 overexpressed tumors were associated with the presence of suspicious calcifications and suspicious axilla. TN tumors were mostly mass lesions, oval, with microlobulated margins, reinforcement, parallel orientation and absence of halo. Regarding survival outcomes, on MMG examination the presence of suspicious microcalcifications reduced OS and CSS rates. The type of shape and margin of the nodules modified the CSS and the axillary status decreased OS, CSS and DFS. On US, non-mass lesions resulted in lower CSS and the type of margin impacted OS and CSS. Heterogeneous lesions demonstrated lower CSS and DFS, while the posterior acoustic effect and axillary status had an impact on OS, CSS and DFS. Conclusion: The breast carcinomas imaging characteristics, evaluated by the mammographic and ultrasonographic BI-RADS ® (5th Edition) descriptors, in addition to being associated with biomarkers and histological subtypes approximated by IHC, also have prognostic value with a direct impact on overall survival, cancer-specific and disease-free survival.
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spelling Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientesAssociation between BI-RADS® mammographic and ultrasound predictors with the breast carcinomas biological aggressivenes and patient survivalCâncer de mamaMamografiaUltrassonografia mamáriaRadiogenômicaSobrevidaObjective: To evaluate the association between imaging characteristics of breast carcinomas (by the BI-RADS ® [5th Edition]) mammographic and ultrasonographic descriptors) and tumor histological characteristics, with the molecular subtypes approximated by immunohistochemistry (IHC) and with the overall survival (OS), Cancer Specific Survival (CCS) and Disease-Free Survival (DFS) of affected patients. Methods: This is a single-center, retrospective cohort. This study included patients diagnosed with invasive breast cancer between 2012 and 2015, age ≥ 18 years, in stages I, II and III. The included patients underwent diagnosis and follow-up at the Hospital das Clínicas de Botucatu, with mammography, ultrasound and histopathological data archived in the Hospital's medical records. Clinical, imaging and anatomopathological data were collected. The association between imaging descriptors, biomarkers and histological subtypes was analyzed. To study the association of variables and compare proportions, the chi-square test was used. The primary outcome was OS and secondary outcomes were DFS and CSS. Kaplan-Meier curve and Cox regression model were used to evaluate the association between imaging descriptors and OS, DFS and CSS. Differences in survival rates were assessed using hazard ratio (HR). In all tests, a significance level of 5% or the corresponding p-value was adopted. Results: The study included 260 women with a mean age of 56.3 ± 12.4 years at diagnosis, mean tumor size of de 2.6cm ±1,63 cm and follow up period of 114 months. The main mammography findings were: nodular lesions were associated with ER -, HER-2 negative and Ki-67 ≥ 20%. The irregular shape was associated with less aggressive lesions (RE+, RP+ and Ki-67 <20%). Round lesions were frequently related to Ki-67≥20%. Regarding the margin, while the circumscribed, microlobulated and obscured margins were linked to hormone receptor negativity, the spiculated margin was more frequent in ER and PR positive carcinomas. HER-2 suppression was more common in indistinct and microlobulated tumors, in the presence of asymmetries and suspicious microcalcifications. Finally, the suspicious axilla was more closely related to ER-, RP-, HER-2 + and high Ki-67. Regarding molecular subtypes, non-mass lesions and nodules with indistinct or microlobulated margins were associated with the hybrid subtype, while triple-negative (TN) tumors were mostly nodular, with an oval or round shape, with a circumscribed or obscured margin. The suspicious axilla in MMG was inversely associated with the Luminal B subtype and directly associated with pure HER-2. Also, in the HER-2 subtype, the presence of suspicious microcalcifications was statistically significant. Regarding ultrasound findings: of the microlobulated tumors, the majority were grade 3. Undifferentiated tumors were also more frequent with heterogeneous echogenicity, parallel orientation, posterior acoustic reinforcement and suspicious axillary lymph nodes. Grade 1 tumors were associated with hypoechogenic, non-parallel lesions, with shadow or combined pattern, with echogenic halo and negative axilla. Grade 2 carcinomas only showed an association with no subsequent effect. ER and PR positive tumors were irregular, with an angled, spiculated or indistinct margin, hypoechoic, non-parallel, with an echogenic halo, with shadow or absence of posterior acoustic effect and with a negative axilla. Negative ER and PR, in turn, presented an oval or round shape, microlobulated margins, heterogeneous echotexture, reinforcement, suspicious axilla on US and an inverse association with the presence of the halo. The mixed effect, despite being related to RE+, was mostly RP-. The PR was also negative in tumors that showed flow on Doppler. Regarding tumors with HER-2 overexpression, the minority had posterior shadowing. As for Ki-67, high rates were associated with oval or round lesions, with microlobulated or angled margins, heterogeneous, reinforcement, Doppler flow and suspicious axilla. Regarding subtypes, Luminal A were irregular, hypoechogenic, non-parallel, without Doppler flow or suspicious microcalcification, with posterior acoustic shadow and negative axilla. Luminal B, in turn, was associated with non-parallel orientation. HER-2 overexpressed tumors were associated with the presence of suspicious calcifications and suspicious axilla. TN tumors were mostly mass lesions, oval, with microlobulated margins, reinforcement, parallel orientation and absence of halo. Regarding survival outcomes, on MMG examination the presence of suspicious microcalcifications reduced OS and CSS rates. The type of shape and margin of the nodules modified the CSS and the axillary status decreased OS, CSS and DFS. On US, non-mass lesions resulted in lower CSS and the type of margin impacted OS and CSS. Heterogeneous lesions demonstrated lower CSS and DFS, while the posterior acoustic effect and axillary status had an impact on OS, CSS and DFS. Conclusion: The breast carcinomas imaging characteristics, evaluated by the mammographic and ultrasonographic BI-RADS ® (5th Edition) descriptors, in addition to being associated with biomarkers and histological subtypes approximated by IHC, also have prognostic value with a direct impact on overall survival, cancer-specific and disease-free survival.Objetivo: O objetivo deste trabalho foi avaliar as características de imagem dos carcinomas de mama associando os descritores mamográficos e ultrassonográficos do BI-RADS ® (5ª Edição) com as características histológicas tumorais, com os subtipos moleculares aproximados pela imunohistoquímica (IHQ) e com a Overall survival (OS), a Cancer–specific survival (CCS) e a Disease-Free Survival (DFS) dos pacientes acometidos. Métodos: Trata-se de um estudo observacional, de coorte retrospectiva. Foram incluídas mulheres diagnosticadas com carcinoma de mama do tipo não especial, entre os anos de 2012 a 2015, com idade ≥ 18 anos, em estádio I, II e III. As pacientes incluídas realizaram o diagnóstico e seguimento no Hospital das Clínicas de Botucatu, tendo os exames de mamografia, ultrassonografia e os dados histopatológicos de seus tumores arquivados no prontuário do Hospital. Foram coletados dados clínicos, imaginológicos e anatomopatológicos. Foi analisada a associação entre os descritores imaginológicos, os biomarcadores e os subtipos histológicos. Para o estudo da associação das variáveis e para a comparação das proporções foi utilizado o teste qui-quadrado. O desfecho primário foi a OS e os desfechos secundários foram DFS e CSS. Curva de Kaplan-Meier e modelo de regressão de Cox foram empregados para avaliar a associação entre os descritores imaginológicos e a OS, DFS e CSS. As diferenças nas taxas de sobrevida foram avaliadas por hazard ratio (HR). Em todos os testes foram adotados o nível de significância de 5% ou o p-valor correspondente. Resultados: Foram incluídas 260 mulheres com média de idade no diagnóstico de 56 anos (desvio padrão - DP de 12,4 anos), com tumores predominantemente ductais, tamanho médio de 2.6cm (DP=1,63 cm) e tempo médio de seguimento de 114 meses. Os principais achados em relação à mamografia foram: enquanto as lesões nodulares se associaram ao RE -, HER-2 negativo e Ki-67 ≥ 20%, as lesões não massa se relacionaram positivamente ao grau 2, ao RE+, ao HER-2 positivo e ao Ki-67<20%. A forma irregular se associou a lesões menos agressivas (RE+, RP+ e Ki-67 <20%). A redonda foi mais frequente apenas em lesões com Ki-67≥20%. Em relação à margem, enquanto as circunscritas, microlobuladas e obscurecidas foram ligadas a negatividade dos receptores hormonais, a espiculada foi mais frequentes em carcinomas com RE e RP positivo. A supexpressão de HER-2 foi mais comum em tumores indistintos e microlobulados, na presença de assimetrias e de microcalcificações suspeitas. Por fim, a axila suspeita teve maior relação com RE-, RP-, HER-2 + e Ki-67 alto. Em relação aos subtipos moleculares, as lesões não massa e nódulos de margem indistintas ou microlobuladas foram associadas ao subtipo híbrido, enquanto os tumores triplo negativos (TN) foram em maioria nodulares, com forma ovalada ou redonda, com margem circunscrita ou obscurecida e pouco frequentes na presença de assimetrias. A axila suspeita na MMG foi inversamente associada ao subtipo Luminal B e diretamente associada aos HER-2 puros. Também no subtipo HER-2, a presença de microcalcificações suspeitas foi estatisticamente significante. Quanto aos achados da ultrassonografia: dos tumores microlobulados, a maioria apresentou grau 3. Tumores indiferenciados também foram mais frequentes na ecogenicidade heterogênea, orientação paralela, reforço acústico posterior e linfonodos axilares suspeitos. Os tumores grau 1 foram associados a lesões hipoecogênicas, não paralelas, com sombra ou padrão combinado, com halo ecogênico e axila negativa. Os carcinomas grau 2 apresentaram apenas associação com efeito posterior ausente. Em relação aos receptores hormonais, os tumores RE e RP positivos foram irregulares, de margem angulada, espiculada ou indistinta, hipoecogênicos, não paralelos, com halo ecogênico, com sombra ou ausência de efeito acústico posterior e com axila negativa. Os RE e RP negativos, por sua vez, apresentaram forma ovalada ou redonda, margens microlobuladas, ecotextura heterogênea, reforço, axila suspeita no US e uma associação inversa com a presença do halo. O efeito misto, apesar de se relacionar com o RE+, foi em maior parte RP-. O RP também foi negativo em tumores que apresentaram fluxo ao doppler. Em relação aos tumores com superexpressão do HER-2, a minoria tinha sombra posterior. Quanto ao Ki-67, altos índices foram associados a lesões ovaladas ou redondas, com margens microlobuladas ou anguladas, heterogêneas, reforço, fluxo ao doppler e axila suspeita. Em relação aos subtipos, os Luminais A foram irregulares, hipoecogênicos, não paralelos, sem fluxo doppler ou microcalcificação suspeitas, com sombra acústica posterior e axila negativa. O luminal B, por sua vez, foi associacado com orientação não paralela. Os tumores HER-2 superexpressos se associaram à presença de calcificações suspeitas e com axila suspeita. Os tumores TN foram em maioria lesões massa, ovaladas, com margens microlobuladas, reforço, orientação paralela e ausência de halo. Quanto aos desfechos de sobrevida, no exame de MMG a presença de microcalcificações suspeitas reduziu as taxas de OS e de CSS. O tipo de forma e de margem dos nódulos modificou a CSS e o status axilar diminuiu OS, CSS e a DFS. No US, as lesões não massa resultaram em menor CSS e o tipo de margem impactou a OS e a CSS. Lesões heterogêneas demonstraram menor CSS e DFS, já o efeito acústico posterior e o status axilar apresentram impacto em OS, CSS e DFS. Conclusão: As características imaginológicas dos carcinomas de mama, traduzidas pelos descritores mamográficos e ultrassonográficos do BI-RADS ® (5ª Edição), além de se associarem com biomarcadores e com os subtipos histológicos aproximado pela IHQ, também apresentam valor prognóstico, com impacto direto em sobrevida global, específica pelo câncer e sobrevida livre de doença.Universidade Estadual Paulista (Unesp)Pessoa, Eduardo Carvalho [UNESP]Vespoli, Heloisa Maria de Luca [UNESP]Pessoa, Carla Priscila Kamyia Carvalho [UNESP]Oliveira, Dênia Reis de Paula [UNESP]2024-05-06T11:07:31Z2024-05-06T11:07:31Z2024-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://hdl.handle.net/11449/25547633004064077P276205083561588420000-0002-9319-9332porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESP2025-10-16T09:00:26Zoai:repositorio.unesp.br:11449/255476Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-10-16T09:00:26Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
Association between BI-RADS® mammographic and ultrasound predictors with the breast carcinomas biological aggressivenes and patient survival
title Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
spellingShingle Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
Oliveira, Dênia Reis de Paula [UNESP]
Câncer de mama
Mamografia
Ultrassonografia mamária
Radiogenômica
Sobrevida
title_short Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
title_full Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
title_fullStr Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
title_full_unstemmed Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
title_sort Associação entre os preditores mamográficos e ultrassonográficos do BI-RADS® com a agressividade biológica dos carcinomas de mama e com a sobrevida das pacientes
author Oliveira, Dênia Reis de Paula [UNESP]
author_facet Oliveira, Dênia Reis de Paula [UNESP]
author_role author
dc.contributor.none.fl_str_mv Pessoa, Eduardo Carvalho [UNESP]
Vespoli, Heloisa Maria de Luca [UNESP]
Pessoa, Carla Priscila Kamyia Carvalho [UNESP]
dc.contributor.author.fl_str_mv Oliveira, Dênia Reis de Paula [UNESP]
dc.subject.por.fl_str_mv Câncer de mama
Mamografia
Ultrassonografia mamária
Radiogenômica
Sobrevida
topic Câncer de mama
Mamografia
Ultrassonografia mamária
Radiogenômica
Sobrevida
description Objective: To evaluate the association between imaging characteristics of breast carcinomas (by the BI-RADS ® [5th Edition]) mammographic and ultrasonographic descriptors) and tumor histological characteristics, with the molecular subtypes approximated by immunohistochemistry (IHC) and with the overall survival (OS), Cancer Specific Survival (CCS) and Disease-Free Survival (DFS) of affected patients. Methods: This is a single-center, retrospective cohort. This study included patients diagnosed with invasive breast cancer between 2012 and 2015, age ≥ 18 years, in stages I, II and III. The included patients underwent diagnosis and follow-up at the Hospital das Clínicas de Botucatu, with mammography, ultrasound and histopathological data archived in the Hospital's medical records. Clinical, imaging and anatomopathological data were collected. The association between imaging descriptors, biomarkers and histological subtypes was analyzed. To study the association of variables and compare proportions, the chi-square test was used. The primary outcome was OS and secondary outcomes were DFS and CSS. Kaplan-Meier curve and Cox regression model were used to evaluate the association between imaging descriptors and OS, DFS and CSS. Differences in survival rates were assessed using hazard ratio (HR). In all tests, a significance level of 5% or the corresponding p-value was adopted. Results: The study included 260 women with a mean age of 56.3 ± 12.4 years at diagnosis, mean tumor size of de 2.6cm ±1,63 cm and follow up period of 114 months. The main mammography findings were: nodular lesions were associated with ER -, HER-2 negative and Ki-67 ≥ 20%. The irregular shape was associated with less aggressive lesions (RE+, RP+ and Ki-67 <20%). Round lesions were frequently related to Ki-67≥20%. Regarding the margin, while the circumscribed, microlobulated and obscured margins were linked to hormone receptor negativity, the spiculated margin was more frequent in ER and PR positive carcinomas. HER-2 suppression was more common in indistinct and microlobulated tumors, in the presence of asymmetries and suspicious microcalcifications. Finally, the suspicious axilla was more closely related to ER-, RP-, HER-2 + and high Ki-67. Regarding molecular subtypes, non-mass lesions and nodules with indistinct or microlobulated margins were associated with the hybrid subtype, while triple-negative (TN) tumors were mostly nodular, with an oval or round shape, with a circumscribed or obscured margin. The suspicious axilla in MMG was inversely associated with the Luminal B subtype and directly associated with pure HER-2. Also, in the HER-2 subtype, the presence of suspicious microcalcifications was statistically significant. Regarding ultrasound findings: of the microlobulated tumors, the majority were grade 3. Undifferentiated tumors were also more frequent with heterogeneous echogenicity, parallel orientation, posterior acoustic reinforcement and suspicious axillary lymph nodes. Grade 1 tumors were associated with hypoechogenic, non-parallel lesions, with shadow or combined pattern, with echogenic halo and negative axilla. Grade 2 carcinomas only showed an association with no subsequent effect. ER and PR positive tumors were irregular, with an angled, spiculated or indistinct margin, hypoechoic, non-parallel, with an echogenic halo, with shadow or absence of posterior acoustic effect and with a negative axilla. Negative ER and PR, in turn, presented an oval or round shape, microlobulated margins, heterogeneous echotexture, reinforcement, suspicious axilla on US and an inverse association with the presence of the halo. The mixed effect, despite being related to RE+, was mostly RP-. The PR was also negative in tumors that showed flow on Doppler. Regarding tumors with HER-2 overexpression, the minority had posterior shadowing. As for Ki-67, high rates were associated with oval or round lesions, with microlobulated or angled margins, heterogeneous, reinforcement, Doppler flow and suspicious axilla. Regarding subtypes, Luminal A were irregular, hypoechogenic, non-parallel, without Doppler flow or suspicious microcalcification, with posterior acoustic shadow and negative axilla. Luminal B, in turn, was associated with non-parallel orientation. HER-2 overexpressed tumors were associated with the presence of suspicious calcifications and suspicious axilla. TN tumors were mostly mass lesions, oval, with microlobulated margins, reinforcement, parallel orientation and absence of halo. Regarding survival outcomes, on MMG examination the presence of suspicious microcalcifications reduced OS and CSS rates. The type of shape and margin of the nodules modified the CSS and the axillary status decreased OS, CSS and DFS. On US, non-mass lesions resulted in lower CSS and the type of margin impacted OS and CSS. Heterogeneous lesions demonstrated lower CSS and DFS, while the posterior acoustic effect and axillary status had an impact on OS, CSS and DFS. Conclusion: The breast carcinomas imaging characteristics, evaluated by the mammographic and ultrasonographic BI-RADS ® (5th Edition) descriptors, in addition to being associated with biomarkers and histological subtypes approximated by IHC, also have prognostic value with a direct impact on overall survival, cancer-specific and disease-free survival.
publishDate 2024
dc.date.none.fl_str_mv 2024-05-06T11:07:31Z
2024-05-06T11:07:31Z
2024-03-01
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 https://hdl.handle.net/11449/255476
33004064077P2
7620508356158842
0000-0002-9319-9332
url https://hdl.handle.net/11449/255476
identifier_str_mv 33004064077P2
7620508356158842
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dc.language.iso.fl_str_mv por
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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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 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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