Estudo das histonas H4K12ac e H3K36me3 em neoplasias da tireóide: comparação entre tipos histológicos e comportamento metastático

Abstract

The preoperative diagnosis of thyroid nodules remains, in some cases, a challenge. At present, fine needle aspiration biopsy, followed by cytology, is the gold standard, but its application is limited. It is therefore extremely motivating the idea to identify molecular changes that can distinguish malignant from benign thyroid nodules. Epigenetic alterations, particularly histone modifications, play an important role in control of gene expression, and cancer cells exhibit alterations in these modifications patterns. Little information about histone modifications in thyroid neoplasms and relationship between such modifications and the tumor aggressiveness is at present available. This study evaluates the expression pattern and biological relevance of histone modifications H4K12ac and H3K36me3, in thyroid tumors and normal thyroid tissues, by immunohistochemistry. Here it is evidenced that, reactivity to H4K12ac is an event observed in all samples of normal thyroid, thyroid carcinomas and adenomas, so it is not possible use this modification as a marker for these neoplasms. The H3K36me3 shows level of staining higher in normal tissue as compared to neoplasms, a fact that suggests a possible role of this histone mark on thyroid tumorigenesis. Unlike other tissues, that show nuclear staining, carcinoma oncocytic exhibits cytoplasmic staining, to both molecules, as well as a higher level for H3K36me3. Association between histones and mitochondrial membrane could be an event that determines such differences.