Alterações moleculares no carcinoma da mama e ovário: expressão de MCT1 e MCT4 e ampliação do HER2
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Data
2009
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O cancro de mama é o cancro mais comum nas mulheres, contando em 32% de todos os casos de cancros femininos. O cancro do ovário conta para 5% de todos os cancros na mulher e por não poderem ser detectados previamente no seu desenvolvimento, entram nas estatísticas desproporcionais dos cancros fatais.
Progressos na biologia molecular resultaram na identificação e no conhecimento de marcadores moleculares que possam ter um prognóstico e um valor preditivo para pacientes com cancro. O HER2/neu é um dos genes mais caracterizados deste tipo de marcadores onde a sua amplificação ocorre em cerca de 30% de cancros de mama e ovário.
O rápido transporte de lactato através da membrana plasmática tem uma importância fundamental para todas as células mamíferas sob condições hipóxicas quando se tornam glicolíticas. O papel fisiológico dos transportadores é primeiriamente transportar os monocarboxilatos endógenos como o piruvato e o lactato. Os transportadores de monocarboxílatos (MCTs) são importantes para a viabilidade das células tumorais sendo conhecido estas serem extremamente glicoliticas, produzindo lactato em excesso, prosperando em condições hipóxicas.
Neste presente trabalho analisou-se a amplificação do gene HER2/neu por “Chromogenic in situ Hybridisation” em carcinomas de mama e ovário bem como a sobrexpressão dos MCTs 1 e 4 por imunohistoquímica nos mesmos tecidos tumorais, utilizando-se para a obtenção das amostras em causa a recente técnica de “Tissue Microarray”. Os resultados obtidos permitiram afirmar que a última técnica é suficientemente representativa para o estudo em questão. Para além disso, evidenciou-se a sobrexpressão do MCT4 em células tumorais de mama, contrariamente ao MCT1. No ovário, não se destacou qualquer sobrexpressão entre os diferentes tipos de carcinomas.
Finalmente, a técnica de CISH foi provada ser uma alternativa para os exames patológicos rotineiros, sobretudo aquando resultados equívocos quer por IHC quer por “Fluorescent in situ Hybridization”.
The breast cancer is the most common cancer in women counting for 32% of all female cancers. The ovary cancer counts for 5% of all women cancers and due to the lack of previous detection, it enters in the disproportional statistics of deadly cancers. Progresses in molecular biology results in the identification and knowledge of molecular markers that can have a prognostic and predictive value for patients with cancer. The HER2/neu gene is the most characterized marker where is amplification occurs in 30% of breast and ovary cancer. The rapid lactate transport through the plasma membrane has a fundamental importance to mammalian cells under hypoxic conditions when they become glycolitic. The physiologic role of transporters is primarily transport endogenous monocarboxylates like piruvate and lactate. The monocarboxylate transporters (MCTs) are important to the viability of tumors cells known has being extremely glycolitic, producing excess of lactate and prospering under hypoxic conditions. In this present work, it has been analyzed the amplification of HER2/neu gene by chromogenic in situ hybridization in breast and ovary carcinomas as well as the overexpression of MCT1 and MCT4 by immunohistochemistry in the same neoplastic tissues. For the preparation of the samples for immunohistochemistry, it has been utilized the recent technique of tissue microarray. The obtained results allowed to affirm that the last technique is representative for the present study. Besides that, it was noticed the MCT4 overexpression in breast tumor cells, contrarily to MCT1. In the ovary, it was not observed any overxpression between the different types of carcinomas. Finally, the CISH technique was proved to be an alternative for pathologic exams, particularly in equivocal results either for IHC and fluorescent in situ hybridization.
The breast cancer is the most common cancer in women counting for 32% of all female cancers. The ovary cancer counts for 5% of all women cancers and due to the lack of previous detection, it enters in the disproportional statistics of deadly cancers. Progresses in molecular biology results in the identification and knowledge of molecular markers that can have a prognostic and predictive value for patients with cancer. The HER2/neu gene is the most characterized marker where is amplification occurs in 30% of breast and ovary cancer. The rapid lactate transport through the plasma membrane has a fundamental importance to mammalian cells under hypoxic conditions when they become glycolitic. The physiologic role of transporters is primarily transport endogenous monocarboxylates like piruvate and lactate. The monocarboxylate transporters (MCTs) are important to the viability of tumors cells known has being extremely glycolitic, producing excess of lactate and prospering under hypoxic conditions. In this present work, it has been analyzed the amplification of HER2/neu gene by chromogenic in situ hybridization in breast and ovary carcinomas as well as the overexpression of MCT1 and MCT4 by immunohistochemistry in the same neoplastic tissues. For the preparation of the samples for immunohistochemistry, it has been utilized the recent technique of tissue microarray. The obtained results allowed to affirm that the last technique is representative for the present study. Besides that, it was noticed the MCT4 overexpression in breast tumor cells, contrarily to MCT1. In the ovary, it was not observed any overxpression between the different types of carcinomas. Finally, the CISH technique was proved to be an alternative for pathologic exams, particularly in equivocal results either for IHC and fluorescent in situ hybridization.
Descrição
Dissertação de Mestrado em Genética Molecular, Comparativa e Tecnológica
Palavras-chave
Biologia molecular , Técnicas genéticas , Gene (HER2) , Neoplasias mamárias , Neoplasias ovarianas , Transportadores monocarboxilatos