Estudo do canibalismo celular e da modificação epigenética da histona H3 em lesões de células gigantes

Abstract

Background: Central giant cell granuloma (CGCG) of the jaws is a benign lesion that exhibits varied clinical behavior, being classified as non-aggressive or aggressive. This research aimed to morphologically evaluate the cell cannibalism and the immunohistochemical expression of the acetylation of histone H3 lysine 9 (H3K9ac) and ING5 in 19 cases of peripheral giant cell granuloma (PGCG), 38 cases of CGCG (19 non-aggressive cases and 19 aggressive cases) and in 19 cases of giant cell tumor (GCT) of bone, as well as to analyze the association of cell cannibalism and this immunoexpression with the clinical behavior of these lesions. Methods: Cell cannibalism analysis was performed through the quantification of cannibal multinucleated giant cells (CMGC). H3K9ac immunoexpression analysis was performed quantitatively in mononuclear cells, multinucleated giant cells (MGC), and CMGC. ING5 immunoexpression was analyzed semiquantitatively in the mononuclear cells and quantitatively in the MGC and CMGC. Data analysis was performed using Student's t-test and Spearman's rank correlation coefficient. Results: A significant great amount of CMGC was observed in aggressive CGCG compared to non-aggressive CGCG (p = 0.044). There were no significant differences in the amount of CMGC between PGCG and non-aggressive CGCG (p = 0.858) and between aggressive CGCG and GCT of bone (p = 0.069). CGCG exhibiting rapid growth, tooth displacement, and/or root resorption had larger amounts of CMGC (p = 0.035; p = 0.041, respectively). MGC and CMGC from aggressive CGCG exhibited overexpression of H3K9ac (p < 0.0001; p < 0.0001, respectively) compared to non-aggressive CGCG. Similarly, aggressive CGCG showed overexpression of ING5 in MGC and CMGC (p < 0.05; p < 0.0001, respectively) when compared to the non-aggressive CGCG. No statistical differences were found among the H3K9ac and ING5 expressions when compared to the aggressive CGCG and GCT of bone (p > 0.05). ING5 high expression was observed in mononuclear cells in all lesions. H3K9ac and ING5 overexpression were associated with aggressive characteristics in CGCG (p < 0.05). Conclusions: Aggressive CGCG shows a great amount of CMGC when compared to non-aggressive CGCC. Thus, its quantification can help to predict CGCG clinical behavior. The significant overexpression of H3K9ac and ING5 may indicate higher clastic activity and cell cannibalism induction in aggressive CGCG and, consequently, be associated with greater aggressiveness in these lesions.