Avaliação imuno-histoquímica de formas modificadas de histonas em queratocistos odontogênicos submetidos à marsupialização

Abstract

The odontogenic keratocyst (OKC) is a cystic, intraosseous, locally aggressive lesion that presents unique histopathological features. Its treatment can be challenging due to the high recurrence rates associated with the lesion. In this sense, one of the described technique for the treatment of OKC is the marsupialization followed by enucleation of the cystic remnants. This modality of treatment causes modifications in the epithelium of the lesion, accompanied by a reduction in its size. The mechanisms that regulate these modifications are not fully elucidated in the literature. Histone proteins act in the formation and maintenance of chromatin. They have an N-terminal tail that allow reversible bonds with the ability to cause silencing and activation of DNA translation. The role of histone modifications in odontogenic keratocysts is not yet known. In the present study, 22 cases of OKC treated by marsupialization and subsequent enucleation were subjected to immunohistochemistry assays to detect the modified histones H3K9ac, H3K9me3, H3K18ac, H3K36me3 and H4K12ac, in addition to the cell proliferation marker Ki-67. There was a significant reduction in the H3K9me3 levels of the final samples (obtained by enucleation) for the altered cystic epithelium in relation to the initial samples (obtained by marsupialization). Significant correlation was also detected between reactivity for Ki-67 and for the modified histones H3K9ac, H4K12ac and H3K36me3 in the final samples with typical OKC epithelium. These results suggest heterochromatin state instability, as well as a loss of repair capacity to DNA damage, arising from marsupialization and mediated by histone modifications, in particular H3K9me3.