Histone 3 Hyperacetylation and the Aggressive Behavior of Giant Cell Lesions

ABSTRACT Introduction Giant Cell Lesions exhibit variable aggressive clinical behavior. Understanding the molecular mechanisms of these lesions can facilitate a more personalized and effective therapeutic approach. Material and Methods The acetylation of Histone H3 at Lysine 9 (H3K9ac) and the expression of Inhibitor of Growth Protein 5 (ING5) were evaluated in 19 cases of Peripheral Giant Cell Granuloma (PGCG), 19 cases of non‐aggressive Central Giant Cell Granuloma (CGCG), 19 cases of aggressive CGCG, and 19 cases of Giant Cell Tumor of Bone (GCTB), totaling 76 cases of Giant Cell Lesions. Results H3K9 hyperacetylation was found in aggressive Giant Cell Lesions compared to non‐aggressive lesions ( p <  0.05). Aggressive Giant Cell Lesions also show higher ING5 expression in multinucleated giant cells and cannibalistic multinucleated giant cells compared to non‐aggressive lesions ( p <  0.05). There was no difference in the levels of H3K9ac and ING5 between aggressive Central Giant Cell Granuloma and Giant Cell Tumor of Bone ( p  > 0.05). H3K9ac and ING5 were associated with aggressive characteristics in the CGCG ( p <  0.05). Conclusion H3K9 hyperacetylation highlights the significance of this epigenetic event in the aggressiveness of Giant Cell Lesions and may indicate their potential for aggressive behavior, thereby providing information to improve treatment strategies, particularly for Central Giant Cell Granuloma. Understanding the CGCG's clinical behavior is essential for determining the therapeutic modality and avoiding long‐term post‐treatment sequelae.