Histone H3K9 Methylation Is Differentially Modified in Odontogenic Cyst and Tumors

Abstract

Objectives Histone modification in odontogenic lesions is mostly unexplored. Trimethylation of histone H3 at lysine residue 9 (H3K9Me3) has been studied in various pathologic conditions and showed biological significance promising for future therapeutic application. This study aimed to investigate the level and clinical relevance of the H3K9Me3 histone modification in odontogenic cysts and tumors. Materials and Methods A total of 105 cases of odontogenic lesions, comprising 30 odontogenic keratocysts (OKCs), 30 adenomatoid odontogenic tumors (AOTs), 30 ameloblastomas, and 15 dental follicles, were included in the study. The paraffin-embedded tissues were immunohistochemically stained for H3K9Me3. Both the intensity and the distribution of staining were evaluated and calculated as H-score. The correlation between the H3K9Me3 expression and the clinical characteristics of each lesion was evaluated. Statistical Analysis The Kruskal–Wallis test followed by Bonferroni's correction was performed to assess the differences in H-score among groups. In addition, Pearson's chi-squared test or Mann–Whitney U test was used to analyze potential factors that could affect protein expression. Results The reduced enamel epithelium of the dental follicle showed uniformly strong H3K9Me3 expression. All odontogenic cysts and tumors examined demonstrated a significantly reduced H3K9Me3 level compared with dental follicles. The AOT showed the lowest H3K9Me3 level, followed by OKC and ameloblastoma. Its immunoreactivity was mainly localized in the basal and parabasal cells of OKC and the whorled/duct-like structures of AOT. Ameloblastoma exhibited marked variation in the H3K9Me3 level among cases. Notably, the upregulated H3K9Me3 was related to multilocularity of OKC and ameloblastoma. Conclusions Histone H3K9 methylation is differentially expressed in odontogenic cysts and tumors. This epigenetic modification may contribute to the pathogenesis and aggressive behavior of odontogenic lesions.