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Master's Dissertation
DOI
https://doi.org/10.11606/D.10.2020.tde-28012020-120135
Document
Author
Full name
Verônica Correia Manoel
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Cogliati, Bruno (President)
Dagli, Maria Lucia Zaidan
Queiroga, Felisbina Luisa Pereira Guedes
Title in Portuguese
Avaliação de marcadores imunohistoquímicos de resistência à múltiplas drogas nos carcinomas mamários em felinos
Keywords in Portuguese
Gatas
Marcadores prognósticos
Oncologia
Tumor de mama
Abstract in Portuguese
O tumor mamário é a terceira neoplasia mais incidente na espécie felina, cerca de 95% dos tumores mamários são malignos e a doença tende a apresentar um comportamento altamente agressivo. O tratamento de eleição para essas neoplasias é a cirurgia radical, seguida de quimioterapia adjuvante. Ainda assim, a mortalidade associada à recidiva tumoral e/ou metástases é frequente, indicando uma falha nos procedimentos terapêuticos, mais precisamente na quimioterapia. Assim, o presente estudo teve como objetivo determinar a imunoexpressão de proteínas associadas à resistência à múltiplas drogas nos carcinomas mamários em felinos, correlacionando-as com aspectos clínico-patológicos e sobrevida. Participaram deste estudo 46 gatas atendidas e operadas em hospitais veterinários públicos e particulares. Os tumores foram submetidos à análise histopatológica, seguida pela análise imunohistoquímica para detecção da glicoproteína P (GlicoP), proteína relacionada a resistência de pulmão (LRP) e metalotioneína (MT). Os parâmetros clinicopatológicos foram correlacionados com a sobrevida pelo teste de Log-rank (P<0,05). A presença de metástase à distância, estadiamento clinico, tipo de cirurgia adotada e o uso de quimioterapia adjuvante apresentaram associação com a sobrevida. A GlicoP e a LRP demonstraram, respectivamente, imunoexpressão intensa em 45,6% e 47,8% dos casos; enquanto a MT apresentou imunoexpressão discreta em 45,7% dos casos. Porém, todas as proteínas foram expressas em algum grau em todas as amostras. Foi encontrada correlação positiva entre a GlicoP e a graduação histológica (P=0,049), e da MT com os subtipos moleculares (P=0,023). Porém, não houve correlação de nenhuma das proteínas analisadas com a sobrevida. Estes dados indicam a presença de múltiplas proteínas de resistência aos antineoplásicos em carcinomas mamários em felinos, além de sua correlação com o alto grau de malignidade destas neoplasias. Apesar de não haver correlação com a sobrevida, estes marcadores podem indicar um pior prognóstico, além de uma possível baixa resposta à quimioterapia adjuvante.
Title in English
Immunohistochemical evaluation of multidrug resistance markers in feline mammary carcinomas
Keywords in English
Mammary tumors
Oncology
Prognostic markers
Queens
Abstract in English
Mammary tumors are ranked as the third neoplasm with most incidents within the feline species. Around 95% of the mammary tumors tend to be malignant and such disease tends to develop an aggressive behavior pattern. In order to treat the neoplasm, radical surgery followed by adjuvant chemotherapy should be performed. Even so, there is a high frequency within the mortality rate and metastasis, point out to some sort of failure related to therapeutical procedures, specifically in chemotherapy. With that, the present case study had the purpose of exposing the immunoexpression related to proteins that are associated with building drug resistance within the mammary carcinoma found in felines. 46 female cats were used in this study and were surgically operated in both publicly and privately owned hospitals. All tumors were submitted into histopathological analysis, followed by immunohistochemistry in order to successfully detect P-Glycoprotein, the protein which is related to the lungs resistance and metalotioneína (MT). The clinical pathological parameters were correlated through the Log-rank (P<0,05) testing. The presence of distant metastasis, hospital admittance, type of surgery performed and the use of adjuvant chemotherapy was directly associated with survival rates. Both GlycoP and LRP showed, respectively, an intense immune expression of 45,6% and 47,8% of all the cases, meanwhile, the MT presented a discrete immune expression on 45.7% of the cases. However, all proteins were expressed within some degree on the scale. It was also noticed that there is a positive correlation between GlycoP and histological graduation (P=0,049), and MT with molecular subtypes (P=0,023). However, there were no correlations found between the studied proteins and survival. The data collected pointed to the presence of multiple types of resistance-related proteins to antineoplastic breast carcinoma found in felines as well as high correlation with the degree of malignancy found in the neoplasm. Even though those were not correlated with survival, these points may lead to a possible worse prognostic, as well as an eventual low positive response to the adjuvant chemotherapy.
 
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Publishing Date
2020-04-15
 
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