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Doctoral Thesis
DOI
10.11606/T.5.2018.tde-22102018-103535
Document
Author
Full name
Tatiana Cristina Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Pereira, Juliana (President)
Bastos, Fernanda Aparecida Nieri
Favero, Cíntia Maria
Marcili, Arlei
Soares, Herbert Sousa
Title in Portuguese
Análise dos tipos histológicos do câncer de mama em cadelas e sua correlação com o perfil de expressão de proteínas associadas ao prognóstico
Keywords in Portuguese
Cães
Imuno-histoquímica
Neoplasias da mama
Patologia
Patologia veterinária
Prognóstico
Abstract in Portuguese
INTRODUÇÃO: Embora os avanços na oncologia sejam significativos, o câncer continua sendo um desafio para a ciência médica. Neste contexto, o diagnóstico precoce assume grande relevância, visto que as ferramentas diagnósticas têm permitido o planejamento terapêutico e a definição mais precisa do prognóstico. Dentre as ferramentas mais utilizadas na Medicina Veterinária destacam-se a histopatologia e a imuno-histoquímica. O presente trabalho, além de definir a casuística das neoplasias mamárias caninas, faz uma comparação entre os resultados histopatológicos e imunohistoquímicos permitindo a definição de assinaturas morfológicas e moleculares associadas a parâmetros de pior prognóstico já definidos pela literatura. MÉTODOS: Foram analisadas 129 amostras parafinadas de carcinoma mamário em cadelas por histopatologia e imuno-histoquímica, correlacionando o perfil de expressão das proteínas COX-2, HER-2, Ki-67 e E-caderina, vimentina e p63 com os subtipos histopatológicos de neoplasias mamárias em cadelas definidos na histopatologia. RESULTADOS: Das 129 amostras 7,7% (10/129) eram não neoplásicas, 7,7% (10/129) eram benignas e 84,5% (109/129) eram malignas. O tipo de tumor mais frequente foi o carcinoma em tumor misto 26,3% (34/129). Das 109 cadelas com tumor mamário maligno, 67 (61,4%) apresentaram tumores grau I, ou de histopatologia mais favorável. Quarenta e dois cães (38,6%) tiveram tumores de grau II e III ou de pior prognóstico histológico. Os tumores de grau III apresentaram maior grau de necrose, infiltração linfocitária, invasão linfática, desmoplasia e microcalcificação que os tumores de grau I e II. Os painéis de expressão proteica revelados pela IHC evidenciaram correlação entre grau histológico e expressão de Ki-67, HER-2, COX-2, p63, vimentina e ecaderina. Considerando os tipos histológicos mais agressivos, como carcinomas sólidos e anaplásicos e carcinosarcoma, observou-se que 66% de carcinomas sólidos, 80% de carcinomas anaplásticos e 66% de carcinosarcomas apresentaram alto índice de proliferação pelo Ki67. Outros marcadores confirmaram a associação desses subtipos histológicos com outras variáveis de IHC de pior prognóstico. CONCLUSÕES: Os resultados deste estudo mostraram uma correlação entre os parâmetros histopatológicos e os marcadores imuno-histoquímicos no tumor de grau I, II e III. No entanto, alguns tumores de grau I podem apresentar um indicador de painel imuno-histoquímico de mau prognóstico e ser subestimados se apenas foram avaliados por histopatologia. Por esta razão, a definição de linhas de tratamento e o prognóstico baseados apenas na análise histopatológica é limitado e deve ser complementado por imuno-histoquímica. Além disso, uma alta prevalência de tumores malignos mamários e a semelhança de tipos histológicos e perfis de coloração imuno-histoquímica qualificam a população canina como modelo promissor para estudos de câncer translacional
Title in English
Analysis on histological types of breast cancer in female dogs and their correlation with the expression profile of proteins associated with prognosis
Keywords in English
Breast neoplasms
Dogs
Immunohistochemistry
Pathology veterinary
Pathology
Prognosis
Abstract in English
INTRODUCTION: Despite significant advances in oncology, cancer remains a challenge for medical science. Early diagnosis is important in this context because the diagnostic tools have enabled therapeutic planning and more precise definition of the prognosis. Histopathology and immunohistochemistry are among the tools most used within veterinary medicine. In addition to defining a sample of cases of canine mammary neoplasia, the present study compared histopathological and immunohistochemical results and thus made it possible to define morphological and molecular signatures that were associated with parameters for worse prognoses that had already been defined in the literature. METHODS: A total of 129 paraffin-embedded mammary carcinoma samples were analyzed histopathologically and immunohistochemically. The expression profiles of the proteins COX-2, HER-2, Ki-67, E-cadherin, vimentin and p63 were correlated with the histopathological subtypes of breast neoplasms in female dogs that were defined. RESULTS: Out of the 129 samples, 7.7% (10/129) were non-neoplastic, 7.7% (10/129) were benign and 84.5% (109/129) were malignant. The most frequent tumor type was mixed-tumor carcinoma, in 26.3% (34/129). Among the 109 female dogs with malignant mammary tumors, 67 (61.4%) presented grade I tumors, or more favorable histopathology. Forty-two (38.6%) had grade II and III tumors or worse histological prognosis. Grade III tumors had higher degrees of necrosis, lymphocytic infiltration, lymphatic invasion, desmoplasia and microcalcification than did grade I and II tumors. The protein expression panels revealed through immunohistochemical analysis showed correlations between histological grade and expression of Ki-67, HER-2, COX-2, p63, vimentin and ecadherin. Among the more aggressive histological types such as solid and anaplastic carcinomas and carcinosarcoma, it was observed that 66% of solid carcinomas, 80% of anaplastic carcinomas and 66% of carcinosarcomas presented high proliferation rates, shown by Ki67. Other markers confirmed the association of these histological subtypes with other immunohistochemical variables for worse prognosis. CONCLUSIONS: The results from this study showed correlations between the histopathological parameters and the immunohistochemical markers in tumors of grades I, II and III. However, it was seen that some grade I tumors with immunohistochemical panels indicating poor prognosis could be underestimated if they were only evaluated by histopathology. For this reason, definition of treatments and prognoses based only on histopathological analysis is limited and should be complemented by immunohistochemistry. In addition, the high prevalence of malignant mammary tumors and the similarity of histological types and immunohistochemical staining profiles qualify the canine population as a promising model for translational cancer studies
 
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Publishing Date
2018-10-24
 
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