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Master's Dissertation
DOI
https://doi.org/10.11606/D.10.2016.tde-31072014-110159
Document
Author
Full name
Lidia Hildebrand Pulz
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Strefezzi, Ricardo de Francisco (President)
Cogliati, Bruno
Xavier, José Guilherme
Title in Portuguese
Imunomarcação de Metaloproteinase 2 e 9 e seus respectivos Inibidores Teciduais como potenciais Indicadores Prognósticos para Mastocitomas Cutâneos Caninos
Keywords in Portuguese
Gelatinases
Imuno-histoquímica
Matriz extracelular
Metástase
Sarcoma de mastócitos
Abstract in Portuguese
Em termos de importância no processo de invasão de tumores e metástases, o desequilíbrio entre a expressão das gelatinases e seus inibidores teciduais resulta em degradação do principal constituinte da matriz extracelular, o colágeno tipo IV, favorecendo os processos de invasão tumoral e metástase. Foram avaliadas 53 lesões de 47 cães submetidos a cirurgia excisional com confirmação diagnóstica de mastocitoma por avaliação histopatológica e imuno-histoquímica para MMP-2, MMP- 9, TIMP-2 e TIMP-1. Os mastocitomas foram classificados em graus I (bem diferenciados), II (moderadamente diferenciados) a III (pouco diferenciados), segundo os critérios estabelecidos por Patnaik, Ehler e Macewen (1984) e as mesmas lesões foram classificadas em alto e baixo grau de malignidade de acordo com o sistema proposto por Kiupel et al. (2011). Os resultados obtidos através da imuno-positividade de mastócitos e leucócitos polimorfonucleraes para as quatro proteínas foram comparados as duas graduações estabelecidas, bem como ao tempo de sobrevida pós-cirúrgica e a mortalidade em função do tumor. Verificou-se que as metaloenzimas e seus inibidores não demonstram nenhum tipo de associação de expressão entre elas. Dentre os marcadores imuno-histoquímicos, a expressão mastocitária de TIMP-1 apresentou associação com o tempo de sobrevida, independente do tratamento quimioterápico adjuvante. Quanto menor a expressão de TIMP-1 nos mastócitos, maiores as taxas de mortalidade e menores os períodos de sobrevida. Enquanto que MMP-2, MMP-9 e TIMP-2 não foram indicadores prognósticos para esta neoplasia. Assim, nossos resultados mostram que o TIMP-1 apresentou-se como bom indicador de sobrevida e, portanto, sugere-se que a utilização deste índice prognóstico adicional a classificação histológica pode aumentar a precisão de prognostico dos mastocitomas em cães auxiliando na adequação de terapias apropriadas
Title in English
Immunostaining of Metalloproteinase 2 to 9 and their respective Tissue inhibitors as potential prognostic indicators for Canine Cutaneous Mast cell tumors
Keywords in English
Extracellular matrix
Gelatinases
Immunohistochemistry
Mast cell sarcoma
Metastasis
Abstract in English
In terms of importance regarding to tumor invasion process and metastasis , the imbalance between the expression of gelatinases and their tissue inhibitors results in degradation of the main constituent of the extracellular matrix, collagen type IV, favoring the processes of tumor invasion and metastasis. Fifty-three lesions, of 47 dogs submitted to surgical excision confirmed the diagnosis of mast cell tumor were evaluated by histopathologic examination and immunohistochemistry for MMP-2, MMP-9, TIMP-2 and TIMP-1. Mast cell tumors were histologically classified as grades I (well differentiated), II (moderately differentiated) to III (poorly differentiated), according to the criteria established by Patnaik, Ehler and MacEwen (1984) and the same lesions were classified as high and low-grade of malignancy according to the system proposed by Kiupel et al. (2011). The results obtained by the immunopositivity of mast cells and polymorphonuclear leukocytes to the four proteins were compared with two established graduations, as well as to post-surgical survival times and mortality due to mast cell disease. It could be verified that metalloenzymes and their inhibitors do not establish any association between the expression of the cell types evaluated. Within the immunohistochemical markers, mast cell expression of TIMP-1 was associated with survival time, independent of adjuvant chemotherapy. The lower the expression of TIMP-1 in mast cells, higher the mortality rates and smaller post-cirurgical survival time. While MMP-2, MMP-9 and TIMP-2 levels were not prognostic indicators for this cancer. Thus, our results show that the TIMP-1 appeared as a good indicator of survival time and therefore it is suggested that the use of this prognostic index as additional histological classification can increase the accuracy of prognosis of mast cell tumors in dogs assisting in the adaptation of appropriate therapies
 
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Publishing Date
2016-04-11
 
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