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https://www.arca.fiocruz.br/handle/icict/31772
THE INVESTIGATION OF TRANSCRIPTIONAL REPRESSION MEDIATED BY ZEB2 IN CANINE INVASIVE MICROPAPILLARY CARCINOMA IN MAMMARY GLAND
Author
Affilliation
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil / Universidade do Oeste de Santa Catarina. Curso de Medicina Veterinária. Campos Novos, SC, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologial. Belo Horizonte, MG, Brasil.
International Center of Research in Cancer. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
International Center of Research in Cancer. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Universidade Federal da Bahia. Escola de Medicina Veterinária. Departamento de Patologia e Clínicas. Salvador, BA, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologial. Belo Horizonte, MG, Brasil.
International Center of Research in Cancer. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
International Center of Research in Cancer. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Universidade Federal da Bahia. Escola de Medicina Veterinária. Departamento de Patologia e Clínicas. Salvador, BA, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Patologia Geral. Belo Horizonte, MG, Brasil.
Abstract
The E-cadherin loss has frequently been associated with transcriptional repression mediated by transcription factors, such as the Zinc Finger E-Box Binding Homeobox-2 (ZEB2). Invasive micropapillary carcinomas (IMPCs) of the breast are aggressive neoplasms frequently related to lymph node metastasis and poor overall survival. In the canine mammary gland, IMPCs has just been reported and, based on its behavioral similarity with the human IMPCs, appears to be a good spontaneous model to this human entity. This study aimed to evaluate the relationship between E-cadherin and ZEB2 in a spontaneous canine model of invasive micropapillary carcinoma of the mammary gland. The correlation among gene expression (ZEB2 and CDH1) and clinicopathological findings was also explored. Nineteen cases of IMPC of the canine mammary gland were obtained, protein and mRNA expression were investigated through immunohistochemistry and RNA In Situ Hybridization, respectively. To better understand the relationship between E-cadherin and ZEB2, immunofluorescence was performed in canine IMPCs. Immunohistochemically, most of IMPCs showed 1+ (14/19, 73.7%) for E-cadherin; and positivity for ZEB2 was diagnosed in 47.4% of the IMPCs. Regarding the RNA In Situ Hybridization (ISH), most of IMPCs showed 4+ and 0+ for E-cadherin (CDH1) and ZEB2 respectively. Through immunofluorescence, the first and second more frequent combinatorial group were E-cadherin+ZEB2- and E-cadherin+ZEB2+; neoplastic cells showing concomitantly weak expression for E-cadherin and positivity for ZEB2 were frequently observed. A negative correlation was observed between E-cadherin and progesterone receptor expression in IMPCs. Based on these results, canine mammary IMPCs show E-cadherin lost and, at times reveals nuclear positivity for the transcription factor ZEB2 that seems to exert transcriptional repression of the CDH1.
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