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Análise da expressão de marcadores da matriz extracelular e de angiogénese em tumores mamários de gata
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Authors
Abstract(s)
Nos últimos anos têm sido realizados estudos clínicos, patológicos e moleculares com o
objectivo de identificar marcadores de prognóstico, bem como possíveis alvos terapêuticos
para o tumor mamário felino (TMF), à semelhança dos procedimentos seguidos atualmente no
tumor mamário da mulher. Entre os marcadores associados ao prognóstico encontram-se as
metaloproteinases de matriz (MMPs), o fator de crescimento do endotélio vascular (VEGF) e
a angiogénese. A participação das MMPs na invasão e metastização tumoral está descrita
tanto em humanos como nos animais domésticos. O VEGF é um fator angiogénico essencial
ao desenvolvimento tumoral e estudos recentes indicam que a sua expressão está
inversamente relacionada com o tempo de sobrevivência. Por sua vez a densidade
microvascular (DMV), que mede a intensidade da angiogénese tumoral através da marcação
de microvasos com anticorpos contra, por exemplo, o fator de von Willebrand (vWF), tem
sido associada à formação de novos vasos, ocorrência de metástases e a um mau prognóstico
no tumor mamário.
Este trabalho pretendeu analisar os níveis de expressão de MMP-2, VEGF e DMV em TMFs
de forma a melhor compreender o seu potencial enquanto marcadores de prognóstico ou
mesmo futuros alvos terapêuticos. Para tal foram avaliados 29 TMFs de vários tipos
histológicos e graus de malignidade no que toca aos níveis expressão destes marcadores, pela
técnica de imunohistoquímica (IHQ). Analisou-se ainda a correlação dos níveis de expressão
destes marcadores com diversos parâmetros clinico-patológicos e imunohistoquímicos.
As principais conclusões retiradas foram que o marcador VEGF parece influenciar
negativamente o tempo de sobrevivência, como também se encontra relacionado com o tipo
histológico. Os resultados obtidos também sugerem que a DMV mostra correlação direta com
o tempo de sobrevivência. Desta forma, percebeu-se que tanto nestes como em outros
marcadores e parâmetros clinico-patológicos avaliados, é essencial vir a estabelecer níveis de
marcação que tenham um real valor prognóstico, de maneira a que futuros pacientes possam
beneficiar de terapêutica dirigida. Apesar dos resultados obtidos serem encorajadores, é
essencial que se continue a testar diferentes protocolos de IHQ, com os mesmos ou diferentes
anticorpos, de forma a otimizar técnicas e possibilitar a reprodutibilidade de resultados
fixando os critérios de avaliação.
ABSTRACT - Evaluation of Extracelular Matrix and Angiogenesis Markers Expression in Feline Mammary Tumours - In the last years an increasing number of clinical, pathological and molecular studies have been published, focused on the identification of prognosis markers, as well as possible therapeutic targets for feline mammary tumour (FMT), similarly to what is done in cases of mammary tumour in women. Among these markers are matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF) and angiogenesis. MMPs’ role in tumours invasion and metastasis has been established in humans and domestic animals. VEGF, an angiogenic factor that is critical in tumour development, was found to be inversely related to survival time. Finally micro-vascular density (MVD), which is a measurement of tumour angiogenesis intensity through the staining of micro-vessels with an antibody against, for example, von Willebrand factor, has been associated with the formation of new blood vessels, metastasis occurrence and prognosis in women with mammary tumours. The presented study aims at analysing MMP-2, VEGF and MVD with the intent of better understanding their potential as prognosis markers or even future therapeutic targets. Thus, the levels of each marker were evaluated in 29 FMTs with different histological and malignancy scores, by immunohistochemistry (IHC) techniques. In addition, the correlation between the expression levels of each marker and several clinical-pathological and immunohistochemical parameters was analysed. This study concluded that the VEGF not only negatively influences the survival time of the patient, but also is related to the histological type of the FMT. Furthermore MVD was proven to positively affect the survival time of queens with mammary tumour. It is now generally accepted that it is essential to establish prognosis value not only for these markers, but also for other markers and clinical-pathological and immunohistochemical parameters, so that future patients may benefit of specific therapy. Despite the encouraging results, it is critical to continue testing other IHC techniques, with the same or different antibodies, with the goal of optimizing procedures making it possible to reproduce results and determine reliable evaluation criteria.
ABSTRACT - Evaluation of Extracelular Matrix and Angiogenesis Markers Expression in Feline Mammary Tumours - In the last years an increasing number of clinical, pathological and molecular studies have been published, focused on the identification of prognosis markers, as well as possible therapeutic targets for feline mammary tumour (FMT), similarly to what is done in cases of mammary tumour in women. Among these markers are matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF) and angiogenesis. MMPs’ role in tumours invasion and metastasis has been established in humans and domestic animals. VEGF, an angiogenic factor that is critical in tumour development, was found to be inversely related to survival time. Finally micro-vascular density (MVD), which is a measurement of tumour angiogenesis intensity through the staining of micro-vessels with an antibody against, for example, von Willebrand factor, has been associated with the formation of new blood vessels, metastasis occurrence and prognosis in women with mammary tumours. The presented study aims at analysing MMP-2, VEGF and MVD with the intent of better understanding their potential as prognosis markers or even future therapeutic targets. Thus, the levels of each marker were evaluated in 29 FMTs with different histological and malignancy scores, by immunohistochemistry (IHC) techniques. In addition, the correlation between the expression levels of each marker and several clinical-pathological and immunohistochemical parameters was analysed. This study concluded that the VEGF not only negatively influences the survival time of the patient, but also is related to the histological type of the FMT. Furthermore MVD was proven to positively affect the survival time of queens with mammary tumour. It is now generally accepted that it is essential to establish prognosis value not only for these markers, but also for other markers and clinical-pathological and immunohistochemical parameters, so that future patients may benefit of specific therapy. Despite the encouraging results, it is critical to continue testing other IHC techniques, with the same or different antibodies, with the goal of optimizing procedures making it possible to reproduce results and determine reliable evaluation criteria.
Description
Dissertação de Mestrado Integrado em Medicina Veterinária
Keywords
Gata Tumores mamários MMP-2 VEGF vWF DMV Imunohistoquímica Prognóstico Queen Mammary tumours Immunohistochemistry Prognosis
Pedagogical Context
Citation
André, J.P.A.V. (2015). Análise da expressão de marcadores da matriz extracelular e de angiogénese em tumores mamários de gata. Dissertação de mestrado. Universidade de Lisboa, Faculdade de Medicina Veterinária, Lisboa.
Publisher
Universidade de Lisboa. Faculdade de Medicina Veterinária