Pesquisa de alvos terapêuticos em tumores do sistema nervoso central do cão: VEGF, Cox-2, c-Kit e EGFR
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2016
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Os tumores gliais e os meningiomas são das neoplasias do sistema nervoso central mais comuns no cão. Mais concretamente, os gliomas refletem 20 a 36% dos tumores primários do SNC em canídeos e os meningiomas ocupam cerca de 22,3 a 59% dos cancros cerebrais caninos. Torna-se cada vez mais importante desenvolver alvos terapêuticos na área da oncologia, essencialmente graças à descoberta de alterações em certas vias de sinalização que podem influenciar o desenvolvimento, a manutenção e a progressão de células cancerígenas. Este estudo teve como objetivo avaliar a imunoexpressão da VEGF e dos recetores EGFR, Cox-2 e c-Kit, com recurso a métodos imunohistoquímicos, e a relação entre a expressão de cada marcador e os tipos tumorais presentes no estudo bem como investigar o potencial destes marcadores como possíveis alvos terapêuticos no tratamento destas neoplasias caninas.
Os resultados desta investigação mostram imunorreatividade para VEGF em todos os subtipos tumorais englobados no nosso estudo, associada a uma intensidade forte na maioria dos casos. Ocorreu positividade para Cox-2 na maioria das amostras estudadas (n=11; 78,6%). Das amostras positivas, 72,7% exibiram imunorreatividade difusa, forte e citoplasmática. A imunomarcação foi positiva para c-kit em mais de 90% das neoplasias estudadas (n=13; 92,9%). Por fim, a imunorreatividade para EGFR foi positiva em grande parte das amostras (n=12; 85,7%) e essencialmente citoplasmática (n=11; 78,6%).
Em conclusão, é possível que as moléculas VEGF, COX-2, c-Kit e EGFR sejam utilizadas como alvos terapêuticos, nomeadamente em meningiomas e oligodendrogliomas. Sendo necessários estudos futuros e um conjunto de amostras representativo para a confirmação destes resultados.
Glial tumours and meningiomas are the most common of central nervous system neoplasia in dogs. Concretely, gliomas reflect 20 to 36% of primary CNS tumours in canids and meningiomas occupy about 22,3 to 59% of canine cerebral cancer subtypes. It is increasingly important the advancement of new therapeutic targets in oncology mainly due to the discovery of changes in certain signalling pathways that may influence the development, maintenance and progression of cancer cells. This study aimed to evaluate the imunoexpression of VEGF and EGFR, COX-2 and c-Kit receptors by immunohistochemical methods and the relation between each marker and cancer subtypes present in the study as well as investigate the markers´ potential as therapeutic targets in the treatment of these canine cancers. The results of this investigation show immunoreactivity to VEGF in all tumour subtypes involved in this study, associated with a strong intensity in most of the cases. Positivity to Cox-2 occurred in the majority of the studied samples (n=11; 78,6%). Of which 72,7% exhibited a strong, diffused, cytoplasmic immunoreactivity. More than 90% of neoplasia analysed had positive immunostaining for c-kit (n=13; 92,9%). Ultimately, EGFR´s immunoreactivity was essentially cytoplasmic and positive in the bulk of the samples (n=12; 85,7%). In conclusion, it is possible that VEGF, COX-2, c-Kit and EGFR molecules can be used as therapeutic targets, namely in meningiomas and oligodendrogliomas. However further studies along with a larger and more representative group sample are mandatory to confirm these findings.
Glial tumours and meningiomas are the most common of central nervous system neoplasia in dogs. Concretely, gliomas reflect 20 to 36% of primary CNS tumours in canids and meningiomas occupy about 22,3 to 59% of canine cerebral cancer subtypes. It is increasingly important the advancement of new therapeutic targets in oncology mainly due to the discovery of changes in certain signalling pathways that may influence the development, maintenance and progression of cancer cells. This study aimed to evaluate the imunoexpression of VEGF and EGFR, COX-2 and c-Kit receptors by immunohistochemical methods and the relation between each marker and cancer subtypes present in the study as well as investigate the markers´ potential as therapeutic targets in the treatment of these canine cancers. The results of this investigation show immunoreactivity to VEGF in all tumour subtypes involved in this study, associated with a strong intensity in most of the cases. Positivity to Cox-2 occurred in the majority of the studied samples (n=11; 78,6%). Of which 72,7% exhibited a strong, diffused, cytoplasmic immunoreactivity. More than 90% of neoplasia analysed had positive immunostaining for c-kit (n=13; 92,9%). Ultimately, EGFR´s immunoreactivity was essentially cytoplasmic and positive in the bulk of the samples (n=12; 85,7%). In conclusion, it is possible that VEGF, COX-2, c-Kit and EGFR molecules can be used as therapeutic targets, namely in meningiomas and oligodendrogliomas. However further studies along with a larger and more representative group sample are mandatory to confirm these findings.
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Dissertação de Mestrado em Biologia Clínica Laboratorial
Palavras-chave
Tumores , Cão