Distribuição do colágeno e dos fibroblastos associados ao câncer nos linfomas caninos
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Data
2018-12-11
Autores
Silva, Maria Claudia Lopes da
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Universidade Estadual Paulista (Unesp)
Resumo
A interação entre células neoplásicas e estroma influencia na gênese, amplificação/ inibição tumoral e cinética das drogas antineoplásicas. O fator de crescimento do endotélio vascular (VEGF) é uma citocina envolvida na angiogênese tumoral, relacionada a sobrevida dos pacientes. Dentre os componentes celulares, os fibroblastos associados ao câncer têm papel fundamental na progressão tumoral e secretam diversas citocinas, incluindo o VEGF. Assim, os objetivos deste trabalho foram caracterizar a distribuição, arranjo e quantidade das fibras de colágeno e reticulina no estroma dos linfomas caninos através dos métodos de Picrosirius Red e reticulina, avaliação imuno-histoquímica dos colágenos tipo I e III, do VEGF e α-SMA. Sessenta linfomas foram agrupados de acordo com o imunofenótipo e grau. O colágeno tipo III foi o predominante. As porcentagens e escores de marcação da reticulina, colágeno e VEGF foram diferentes entre os grupos e imunofenótipos, sendo que o linfoma T de alto grau exibiu os maiores níveis tanto de colágeno, reticulina e VEGF. Houve correlação entre expressão de VEGF e índice proliferativo. A expressão de α-SMA foi semelhante entre os grupos, imunofenótipos e graus. Como conclusão, a maior densidade de componentes fibrosos e níveis de expressão de VEGF nos linfomas T poderia, ao menos em parte, contribuir para o pior prognóstico apresentado por pacientes com esse tipo de tumor. Ainda, o VEGF tem potencial como marcador prognóstico no linfoma canino e o uso de fármacos anti-angiogênicos deveria ser avaliado levando-se em consideração o imunofenótipo e grau e provavelmente seria mais eficaz em animais com linfomas T.
Neoplastic cells interaction with stroma influences tumorigenesis, amplification or inhibition of tumor progression and anticancer drugs kinetics. Vascular endothelial growth factor (VEGF) is a crucial cytokine implicated in tumoral angiogenesis and survival and among cellular components cancer associated fibroblasts play a role on tumour progression, secreting various cytokines, including VEGF. Therefore, the aim of this study was to characterize fibres distribution, arrangement and amount on stroma evaluated in Picrosirius Red and reticulin stained slides as well as in type I and III immunolabelled sections of canine lymphoma, in addition to the immunoexpression of VEGF and α-SMA on neoplastic lymphoma cells and stroma, respectively. Sixty lymphomas were divided into four groups according to immunophenotype and grade. Type III was the preponderant collagen. Staining percentage and scores of reticulin and collagen, as well as scores of VEGF immunolabelling, were significantly different between groups and immunophenotypes, with high-grade T-cell lymphomas exhibiting the largest quantities. Additionally, VEGF was positively correlated with proliferation index. There was no difference regarding α-SMA expression within groups, immunophenotypes or grades. In conclusion, the greater density of fibrous components on T-cell lymphomas, combined with bigger VEGF levels, could, at least partially, explain the poorer prognosis for patients presenting those tumours. Furthermore, VEGF has potential as a prognostic marker for canine lymphoma, and the use of anti-angiogenic drugs should be investigated taking into account immunophenotype and grade and animals with high-grade T-cell tumours would probably benefit more from its use.
Neoplastic cells interaction with stroma influences tumorigenesis, amplification or inhibition of tumor progression and anticancer drugs kinetics. Vascular endothelial growth factor (VEGF) is a crucial cytokine implicated in tumoral angiogenesis and survival and among cellular components cancer associated fibroblasts play a role on tumour progression, secreting various cytokines, including VEGF. Therefore, the aim of this study was to characterize fibres distribution, arrangement and amount on stroma evaluated in Picrosirius Red and reticulin stained slides as well as in type I and III immunolabelled sections of canine lymphoma, in addition to the immunoexpression of VEGF and α-SMA on neoplastic lymphoma cells and stroma, respectively. Sixty lymphomas were divided into four groups according to immunophenotype and grade. Type III was the preponderant collagen. Staining percentage and scores of reticulin and collagen, as well as scores of VEGF immunolabelling, were significantly different between groups and immunophenotypes, with high-grade T-cell lymphomas exhibiting the largest quantities. Additionally, VEGF was positively correlated with proliferation index. There was no difference regarding α-SMA expression within groups, immunophenotypes or grades. In conclusion, the greater density of fibrous components on T-cell lymphomas, combined with bigger VEGF levels, could, at least partially, explain the poorer prognosis for patients presenting those tumours. Furthermore, VEGF has potential as a prognostic marker for canine lymphoma, and the use of anti-angiogenic drugs should be investigated taking into account immunophenotype and grade and animals with high-grade T-cell tumours would probably benefit more from its use.
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Palavras-chave
Linfoma, Cão, Estroma, Imuno-histoquímica, Lymphoma, Dog, Stroma, Immunohistochemistry