Imunoexpressão de CXCL12 e CXCR4 em lesões de células gigantes

Abstract

Giant cell lesions represent a set of pathological processes with similar histopathological features and varied biological behaviors. Despite intense scientific investigation, several aspects related to the pathogenesis and biological behavior of these lesions, with emphasis on the central giant cell lesion (CGCL), the peripheral giant cell lesion (PGCL) and the giant cell tumor (GCT), remain incompletely understood. In the development of several diseases, research has highlighted the participation of a family of low molecular weight proteins, called chemokines, and their receptors. Considering the pathological processes that affect bones, studies have demonstrated the involvement of the chemokine CXCL12 and the CXCR4 receptor in the migration of osteoclast precursor cells, osteoclastogenesis and bone resorption. However these important findings, little is known about the participation of these proteins in giant cell lesions. Thus, the present study aimed to evaluate the immunoexpression of CXCL12 and CXCR4 in CGCL, PGCL and GCT. The sample consisted of 10 cases of aggressive CGCL, 10 cases of non-aggressive CGCL, 10 cases of PGCL and 10 cases of GCT. The cases of LCCG and LPCG came from the archives of the Laboratories of Oral Histopathology of the Departments of Dentistry at the State University of Paraíba (UEPB) and the Federal University of Rio Grande do Norte (UFRN). Regarding the GCT cases, they were selected from the cases filed at the Getúlio Sales Diagnostics Laboratory (Natal, RN, Brazil). Only cases of CLCG with clinical and radiographic information that allowed classification into aggressive or non-aggressive lesions were included, according to criteria described by Chuong et al. (1986). In the immunohistochemical study, the percentages of cytoplasmic (CXCL12 and CXCR4) and nuclear (CXCR4) positivity in mononuclear cells (MC), non-cannibalistic multinucleated giant cells (ncMGC) and cannibalistic multinucleated giant cells (cGMC) were established in 5 fields of greater immunoreactivity (400×). The data obtained were statistically analyzed using the Mann-Whitney and Spearman correlation tests (p<0.05). Low median percentages of positivity for CXCL12 were found in all cell types, with no significant differences between groups (p > 0.05). Cytoplasmic expression of CXCR4 was observed in all groups evaluated, with high median percentages of positivity in ncGMC and cGMC. In MC, GCT exhibited higher cytoplasmic expression of CXCR4 when compared to PGCL (p = 0.007) and non-aggressive CGCL (p = 0.008). Regarding nuclear expression. of CXCR4, all groups showed low percentages of positivity. Compared with PGCL, GCT exhibited a higher median percentage of nuclear positivity for CXCR4 in MC (p = 0.022). Positive correlations were found between cytoplasmic and nuclear immunoexpression of CXCR4 in MC in non-aggressive CGCL (r = 0.914; p < 0.001), in PGCL (r = 0.882; p = 0.001) and in GCT (r = 0.867; p = 0.001). The results suggest a potential involvement of CXCR4 in the pathogenesis of CGCL, PGCL and GCT, possibly by ligand-independent cytoplasmic functions. This chemokine receptor could also contribute to differences in the biological behavior of CGCL. On the other hand, the relevance of CXCL12 in the development of the studied giant cell lesions can be variable.