Imunoexpressão de CXCL12 e CXCR4 em cistos radiculares, cistos dentígeros e ceratocistos odontogênicos

Abstract

Radicular cyst (RC), dentigerous cyst (DC) and odontogenic keratocyst (OKC) are the most frequently occurring odontogenic cysts in the oral and maxillofacial region, but several aspects related to the pathogenesis and biological behavior of these lesions remain incompletely understood. In this scenario, studies have suggested that chemokines and their receptors, especially CXCL12 and CXCR4, may be important in the pathogenesis of inflammatory odontogenic cysts. So far, however, little is known about the expression of these proteins in developmental odontogenic cysts. Thus, this study aimed to evaluate the immunoexpression of CXCL12 and CXCR4 in RCs, DCs and OKCs. The sample consisted of 20 RCs, 20 DCs and 20 OKCs. Clinical data (sex, age and anatomical location of the lesions) were collected from biopsy request forms. In the morphological study, the pattern of the epithelial lining (MOREIRA et al., 2000) and the intensity of the inflammatory infiltrate (PEIXOTO et al., 2012) in RCs were evaluated, as well as the presence of satellite cysts and epithelial budding in OKCs (MYOUNG et al., 2001). For the immunohistochemical study, at 400 magnification, the percentages of cells with cytoplasmic (CXCL12 and CXCR4) and nuclear (CXCR4) positivity in 10 microscopic fields of the epithelial lining and fibrous capsule (BRITO et al., 2018) were determined. The data obtained were submitted to statistical analysis using the Mann-Whitney and Spearman correlation tests (p < 0.05). There was a higher frequency of RCs with inflammatory infiltrate grade III (65.0%) and with hyperplastic epithelial lining (55.0%). Regarding OKCs, no satellite cysts or epithelial budding were found in any of the cases evaluated. In immunohistochemical analysis, a lower percentage of epithelial positivity for CXCL12 was found in OKCs when compared to DCs (p < 0.001) and RCs (p = 0.001). In the fibrous capsule, DCs showed higher immunoexpression of CXCL12 compared with RCs (p = 0.004) and OKCs (p = 0.042). Regarding CXCR4, a lower percentage of cytoplasmic positivity was observed in the epithelial component of OKCs when compared to RCs (p < 0.001) and DCs (p < 0.001). There were no statistically significant differences in the percentages of nuclear positivity for CXCR4, in the epithelial lining, between RCs, DCs and OKCs (p > 0.05). In the fibrous capsule, OKCs showed lower percentages of cytoplasmic positivity for CXCR4 when compared to DCs (p = 0.007) and RCs (p = 0.022). Analysis of the nuclear expression of CXCR4 in the fibrous capsule revealed a higher percentage of positivity in DCs when compared to OKCs (p = 0.007). No significant differences were found in the expressions of CXCL12 and CXCR4 regarding the morphological characteristics of RCs (p > 0.05). In RCs, positive correlations were identified between the cytoplasmic and nuclear expressions of CXCR4, both in the epithelial lining (r = 0.597; p = 0.005) and in the fibrous capsule (r = 0.555; p = 0.011). In addition, in the fibrous capsule of RCs, there was a positive correlation between the expression of CXCL12 and the nuclear expression of CXCR4 (r = 0.523; p = 0.018). In DCs, there was a correlation between the cytoplasmic and nuclear expressions of CXCR4, both in the epithelial lining (r = 0.678; p = 0.001) and in the fibrous capsule (r = 0.937; p < 0.001). In OKCs, a positive correlation was observed between the cytoplasmic and nuclear expressions of CXCR4 in the fibrous capsule (r = 0.796; p <0.001). The results of this study suggest an important participation of chemokine CXCL12 and its receptor CXCR4 in the pathogenesis of RCs, DCs, and OKCs. These proteins may be particularly relevant in the development of odontogenic cysts with less aggressive biological behavior.