Imunoexpressão de Proteínas Relacionadas à Autofagia em Lesões Centrais e Periféricas de Células Gigantes

Abstract

Central giant cell lesions (CGCL) and peripheral giant cell lesions (PGCL) have similar histopathological characteristics, with emphasis on the presence of multinucleated giant cells (MGC) similar to osteoclasts and mononuclear cells (MC). Despite this, these lesions exhibit important differences in terms of etiopathogenesis and biological behavior. Despite intense scientific investigation, the mechanisms responsible for such differences remain incompletely understood. In physiological and pathological processes that involve the modulation of osteoclast and osteoblast functions, research has highlighted the importance of autophagy. Autophagy consists of a catabolic intracellular mechanism, aimed at cell survival, which involves the participation of several molecules, with emphasis on Atg7, LC3A, LC3B, p62 and p-mTOR proteins. Despite the relevant roles of autophagy in several pathological processes, including metabolic and degenerative bone diseases, little is known about its participation in the pathogenesis of giant cell lesions. Thus, the present study aimed to evaluate the immunoexpression of proteins related to autophagy (Atg7, LC3A, LC3B, p62 and p-mTOR) in PGCL and CGCL. The sample consisted of 10 cases of CGCL, 10 cases of non-aggressive CGCL and 10 cases of aggressive CGCL. In the clinical study, CGCL were classified as non-aggressive or aggressive, based on the criteria described by Chuong et al. (1986). In the immunohistochemical study, the percentages of positive MC, cannibal MGC (cMGC) and non-cannibal MGC (ncMGC) (cytoplasm and nucleus) were established in 5 fields of greater immunoreactivity (400x) to antibodies. The data obtained were statistically analyzed using the Mann-Whitney and Spearman correlation tests (p<0.05). Cytoplasmic expression of Atg7, LC3A, LC3B and p62 was found in all groups of lesions and cell types analyzed, with high median percentages of positivity. In MC, aggressive CGCL showed higher Atg7 expression compared to non-aggressive CGCL (p=0.041). For LC3A, non-aggressive CGCL showed lower immunoreactivity in MC when compared to PGCL (p=0.041) and aggressive CGCL (p=0.049). Compared to non-aggressive CGCL, PGCL exhibited higher immunoexpression of LC3B and p62, both in MC (p=0.007; p=0.034, respectively) and in ncMGC (p=0.034; p=0.034, respectively). All groups had low median percentages of p-mTOR positivity in both MC and MGC. Compared to non-aggressive CGCL, PGCL showed higher p-mTOR expression in cMGC (p=0.036). Regarding the nuclear expression of Atg7, LC3A and p-mTOR, all groups showed low median positivity percentages. In CM, aggressive CGCL showed greater positivity for Atg7 compared to PGCL (p=0.005). For LC3A, PGCL showed higher nuclear expression in cMGC compared to aggressive CGCL (p=0.036). In turn, in all groups of lesions and cell types, there was a higher nuclear expression of LC3B and p62 compared to other proteins related to autophagy. In MC, PGCL exhibited greater immunoreactivity for LC3B when compared to non-aggressive CGCL (p=0.049). In all groups, statistically significant correlations were found between immunoexpressions of proteins related to autophagy (p<0.05). In conclusion, the results of this study suggest a potential involvement of autophagy in the pathogenesis of PGCL and CGCL. Differences in the biological behavior of aggressive and non-aggressive LLCG, however, appear to be unrelated to this intracellular catabolic mechanism. Furthermore, through nuclear functions not necessarily related to autophagy, the LC3B and p62 proteins may contribute to the development of PGCL and CGCL.