Análise imunoistoquímica de proteínas relacionadas à autofagia (Atg7, p62 e p-mTOR) em ceratocistos odontogênicos isolados e associados à Síndrome de Gorlin

Abstract

Autophagy is an intracellular degradation mechanism that acts on several physiological and pathological processes, involving the activation of a series of proteins, especially Atg7, p62 and mTOR. Evidence suggests a significant participation of autophagy in the development of odontogenic cysts and tumors, but little is known about its involvement in the pathogenesis of odontogenic keratocysts (OKCs). In the context of odontogenic lesions, OKCs are characterized by a potentially aggressive behavior, with a tendency to recurrence, and by association with Gorlin syndrome. Thus, the present study aimed to evaluate the immunohistochemical expression of autophagy-related proteins (Atg7, p62 and p-mTOR) in odontogenic keratocysts associated with Gorlin syndrome (SOKCs) and non-syndromic odontogenic keratocysts (NSOKCs). The sample consisted of 24 SOKCs and 24 NSOKCs. The immunoexpression of Atg7, p62 and p-mTOR was evaluated in the epithelial component of the lesions, determining the percentages of positive (nuclear and cytoplasmic) cells and the predominance of immunoreactivity in the epithelial layers. The data obtained were statistically analyzed using non-parametric Mann-Whitney and Wilcoxon tests. In all cases studied, nuclear and cytoplasmic expression of Atg7 was observed, with predominance of immunoreactivity in the basal/parabasal layer. Similarly, all cases were immunopositive (nucleus and cytoplasm) for p62, with predominance of parabasal/superficial layer immunoreactivity. In turn, all OKCs showed cytoplasmic labeling of p-mTOR with predominance of immunoreactivity in superficial layers, while nuclear positivity was found in 15 (62.5%) NSOKCs and 14 (58.3%) SOKCs. SOKCs exhibited higher nuclear immunoexpression of p62 (p < 0.001) and Atg7 (p < 0.001) when compared to the NSOKCs. There was no significant difference between the groups of OKCs in the cytoplasmic expression of p62 (p = 0.651) and nuclear p-mTOR (p = 0.717). On the other hand, SOKCs exhibited higher cytoplasmic expression of Atg7 (p < 0.001) and p-mTOR (p = 0.023) when compared to NSOKCs. In the intragroup comparisons, cytoplasmic expressions of Atg7 (p < 0.001) and p-mTOR (p < 0.001) were observed significantly higher than the nuclear ones in both the SOKCs and the NSOKCs. In contrast, nuclear immunoexpression of p62 was greater than the cytoplasmic in SOKCs (p < 0.001). The results suggest a potential role of autophagy in the pathogenesis of OKCs. The biological behavior of SOKCs probably correlates with the activation of autophagy in basal/parabasal layer of epithelial lining, represented by the higher cytoplasmic expression of Atg7 and the lower immunopositivity of the autophagic inhibitor p mTOR in the cytoplasm. In addition, the greater nuclear translocation of the p62 protein in the epithelial component could contribute to the differences in the behavior of SOKCs, possibly through functions not related to autophagy.