Avaliação das modificações pós-traducionais de histonas H3K9me3 e H3K36me3 em leucoplasias bucais

Abstract

Introduction: The pathogenesis of oral leukoplakia (OL) is poorly understood, although genetic and epigenetic events have been indicated as protagonists of the process. The aim of this study was to evaluate the presence of post-translational histone modifications (PTHM) H3K9me3 and H3K36me3 in oral leukoplakias and their association with clinical-pathological data. Methodology: OL cases were selected for the analysis of H3K9me3 (n = 31) and H3K36me3 (n = 32) expression, from which clinical-pathological data were collected: age, gender, location, size, clinical type, smoking habit and malignant transformation. Samples were classified into high risk (HRL) and low risk (LRL) lesions, according to the criterion of Kujan et al. (2006). The immunohistochemical assay was based on the streptavidin-biotin-peroxidase technique, and an immunocolorimetric evaluation of protein expression was performed considering the percentage of nuclei using the ImageJ program. Data were analyzed by parametric and nonparametric tests with two or three comparisons and association tests, with the aid of GraphPad Prism software, version 5. Results: A higher expression of H3K9me3 was observed in OL compared to control (p = 0.0061); In a similar comparison, the expression for H3K36me3 was lower in OL (p = 0.0119). In normal (control) tissue, H3K36me3 was higher than H3K9me3 (p = 0.0026). Higher H3K9me3 expression was noted in OL detected in upper and lower alveolar ridges (p = 0.0076); lesions classified as LRL presented higher H3K9me3 expression than HRL (p = 0.0161). Female patients present higher immunostaining of H3K36me3 (p = 0.0044). Most cases of high expression of H3K9me3 were observed in LRL (p = 0.0038), while H3K36me3 was highly expressed in females (p = 0.0307). Conclusion: The studied modifications H3K9me3 and H3K36me3 play a significant role in the pathogenesis and progression of the OL, being influenced by the lesion location, patient gender and changes in malignant transformation factors.