Análise da ocorrência de metástase intraocular e pulmonar em cadelas portadoras de carcinoma mamário e correlação com mutação e expressão de E-caderina

• Ano de defesa: 2015
• Autor(a) principal: Pardini, Luciana Moura Campos [UNESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Mamas - Doenças; Cães - Doenças; Moleculas de adesão celular; Metastase; Breast - Diseases
• Link de acesso: http://hdl.handle.net/11449/138407; http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/09-05-2016/000858239.pdf

Introduction: E-cadherin is a transmembrane protein, encoded by CDH1 gene, that has an important role in intercellular adhesion of epithelial tissues. Loss of function or decreased expression of E-cadherin may lead to cancer progression and metastasis. In mammary epithelial neoplasms, lung metastases occur more frequently, but the ocular metastasis, especially in the choroid, are relatively common but underdiagnosed clinically. Methods: Twenty-eight dogs of different breeds, non-castrated, older than five years, diagnosed with breast cancer by cytopathological examination, without pulmonary and/or ocular metastasis, have undergone to radical mastectomy and ovariosalpingohisterectomy (OSH), and re-evaluated after three and six months postoperatively. The pattern of relative expression of CDH1 gene in normal and tumor tissues was assessed by TaqMan Universal PCR Master Mix system; the pattern of methylation was performed using MSP-PCR; DNA sequencing analysis of mutations and polymorphisms were performed from peripheral blood using the termination chain reaction technique with BigDye Terminator v.3 Cycle Sequencing kit. Immunohistochemical analyzes were performed to evaluate the expression of E-cadherin. Results: None of the 28 dogs studied had ocular or pulmonary metastasis with 3 or 6 months postoperatively. In 57,1% of cases a decreased relative expression of CDH1 gene was identified. In 100% of cases there was methylated status for the CDH1 gene, confirming the hypothesis that non-tumor cells can contribute to these results. In 46,5% of the cases reduced E-cadherin expression by immunohistochemistry was identified. Three tumor histotypes were identified: complex carcinoma, tubulopapillary, and carcinoma in mixed tumor. In 100% of cases of tubulopapillary carcinoma was identified a reduced gene expression of CDH1 by both qPCR and by immunohistochemistry. The sequencing of the gene, 6 animals (21,4%) had silent mutations in exons 3, 7 ...