Classificação fenotípica prognóstica para neoplasmas mamários em cadelas
Arquivos
Data
2016-11-16
Autores
Varallo, Giovanna Rossi [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer de mama é uma doença heterogênea. Em mulheres está estabelecido um perfil imuno-histoquímico para utilização na rotina clínica de pacientes com câncer de mama. Os fenótipos luminal A, luminal B, HER2 superexpresso e triplo negativo apresentam diferenças prognósticas e preditivas. Entretanto, para a neoplasmas mamários em cadelas, não há uma classificação fenotípica definida. As diferenças prognósticas entre os fenótipos são atribuídas às assinaturas do tumor. Os estudos gênicos possibilitam averiguar o perfil genético da doença e a identificação de novos marcadores moleculares. O objetivo do estudo foi propor uma classificação fenotípica para a determinação de quatro fenótipos: luminal A, luminal B, HER2 superexpresso e triplo negativo, bem como avaliar a imunoexpressão dos marcadores anti-E-caderina, anti-claudinas 1, 3, 4, 7 e do anti-CD24 e anti-CD44. Na segunda etapa do estudo, objetivou-se avaliar o perfil de expressão gênica global dos carcinomas de mama e a diferença de expressão gênica entre os grupos fenotípicos. Para a avaliação imunohistoquímica, o grupo experimental foi composto por 110 amostras de câncer de mama dispostas em lâminas de tissue microarray. Obteve-se 42 tumores luminal A, 41 luminal B, 17 triplo negativo e 10 HER2 superexpresso. Constatou-se que estes últimos apresentam fenótipos mais agressivos e com menores sobrevidas. A expressão positiva da E-caderina foi mais acentuada nos grupos luminal A e luminal B, já a negativa no triplo negativo e no HER2 superexpresso. O padrão das expressões das claudinas 1, 3, 4 e 7 foi semelhante entre os subfenótipos. As células-tronco tumorais foram relacionadas aos graus histológicos mais agressivos (II e III). Para a avaliação da expressão gênica foram usadas 12 amostras de carcinoma mamário de cadelas e quatro mamas normais. Não foi evidenciada diferença na expressão gênica entre os grupos luminal A, luminal B, HER2 superexpresso e triplo negativo pelo microarranjo. O perfil gênico global das neoplasias estudadas mostrou 878 genes superexpressos e 821 genes subexpressos. A análise de enriquecimento aplicada aos genes superexpressos apontou o gene HYAL-1 como um potencial marcador diagnóstico e de recidiva. O PCR confirmou esse resultado. Conclui-se que a classificação molecular é uma ferramenta importante para a avaliação prognóstica dos pacientes com neoplasmas mamários. O gene HYAL-1 diferencialmente expresso participa da via de sinalização metabólica relacionada à carcinogênese mamária e a superexpressão está relacionada com o desenvolvimento do câncer e à recidiva.
The mammary cancer is a heterogeneous disease. In women, an immunohistochemical profile is established for use in the clinical routine of patients with breast cancer. The luminal A, luminal B, HER2 overexpressed and triple negative phenotypes present prognostic and predictive differences. However for mammary neoplasms in bitches, there is no definite phenotypic classification. Prognostic differences between phenotypes are attributed to tumor signatures. Genetic studies make it possible to ascertain the genetic profile of the disease and the identification of new molecular markers. The objective of the study was to propose a phenotypic classification for the determination of four phenotypes in bitches: luminal A, luminal B, HER2 overexpressed and triple negative, as well as to evaluate the immunoexpression of the anti-E-cadherin, anti-claudin markers 1, 3, 4, 7 and anti-CD24 and anti-CD44. In the second stage of the study, the objective was to evaluate the overall gene expression profile of mammary carcinomas and the difference in gene expression between the phenotypic groups. For the immunohistochemical evaluation, the experimental group consisted of 110 mammary cancer samples arranged in tissue microarray slides. 42 luminal A, 41 luminal B, 17 triple negative and 10 HER2 superexpressed tumors were obtained. It was verified that the latter present more aggressive phenotypes and with lower survival rates. Positive expression of E-cadherin was more pronounced in the luminal A and luminal B groups, whereas the negative expression in triple negative and HER2 overexpressed. The standard expression of claudins 1, 3, 4 and 7 was similar among subphenotypes. Tumor stem cells were related to the most aggressive histological grades (II and III). For the evaluation of gene expression, 12 samples of mammary carcinoma of bitches and four normal breasts were used. There was no difference in gene expression between the luminal A, luminal B, HER2 superexpressed and triple negative groups by the microarray. The overall gene profile of the neoplasms studied showed 878 overexpressed genes and 821 underexpressed genes. The enrichment analysis applied to the overexpressed genes pointed to the HYAL-1 gene as a potential diagnostic and relapse marker. PCR confirmed this result. It is concluded that molecular classification is an important tool for the prognostic evaluation of patients with breast neoplasms. The differentially expressed HYAL-1 gene participates in the metabolic signaling pathway related to mammary carcinogenesis and overexpression is related to the development of cancer and relapse.
The mammary cancer is a heterogeneous disease. In women, an immunohistochemical profile is established for use in the clinical routine of patients with breast cancer. The luminal A, luminal B, HER2 overexpressed and triple negative phenotypes present prognostic and predictive differences. However for mammary neoplasms in bitches, there is no definite phenotypic classification. Prognostic differences between phenotypes are attributed to tumor signatures. Genetic studies make it possible to ascertain the genetic profile of the disease and the identification of new molecular markers. The objective of the study was to propose a phenotypic classification for the determination of four phenotypes in bitches: luminal A, luminal B, HER2 overexpressed and triple negative, as well as to evaluate the immunoexpression of the anti-E-cadherin, anti-claudin markers 1, 3, 4, 7 and anti-CD24 and anti-CD44. In the second stage of the study, the objective was to evaluate the overall gene expression profile of mammary carcinomas and the difference in gene expression between the phenotypic groups. For the immunohistochemical evaluation, the experimental group consisted of 110 mammary cancer samples arranged in tissue microarray slides. 42 luminal A, 41 luminal B, 17 triple negative and 10 HER2 superexpressed tumors were obtained. It was verified that the latter present more aggressive phenotypes and with lower survival rates. Positive expression of E-cadherin was more pronounced in the luminal A and luminal B groups, whereas the negative expression in triple negative and HER2 overexpressed. The standard expression of claudins 1, 3, 4 and 7 was similar among subphenotypes. Tumor stem cells were related to the most aggressive histological grades (II and III). For the evaluation of gene expression, 12 samples of mammary carcinoma of bitches and four normal breasts were used. There was no difference in gene expression between the luminal A, luminal B, HER2 superexpressed and triple negative groups by the microarray. The overall gene profile of the neoplasms studied showed 878 overexpressed genes and 821 underexpressed genes. The enrichment analysis applied to the overexpressed genes pointed to the HYAL-1 gene as a potential diagnostic and relapse marker. PCR confirmed this result. It is concluded that molecular classification is an important tool for the prognostic evaluation of patients with breast neoplasms. The differentially expressed HYAL-1 gene participates in the metabolic signaling pathway related to mammary carcinogenesis and overexpression is related to the development of cancer and relapse.
Descrição
Palavras-chave
Cadelas, Classificação, Expressão gênica, HYAL-1, Neoplasias da mama, Prognóstico, Dogs, Classification, Gene expression, Mammary cancer, Prognosis