Imunoexpressão de CXCL12 e CXCR4 em ceratocistos odontogênicos isolados e associados à Síndrome de Gorlin-Goltz

Abstract

Odontogenic keratocyst (OKC) has infiltrative potential, high recurrence and mutations in the PTCH1 tumor suppressor gene, besides the capacity of association to the Gorlin-Goltz syndrome, where the syndromic OKCs are potentially more aggressive. These characteristics have influenced the search for information on the etiopathogenesis of this injury, through protein and molecular markers that aim to improve the understanding of its biological behavior, but there is still much to be clarified. CXCL12 chemokine (SDF-1) and its CXCR4 primary receptor regulate important events in the pathogenesis of various injuries. This paper was intended to analyze the CXCL12 and CXCR4 immunoexpression in isolated and syndromic OKCs. The sample was composed of 21 cases of isolated OKCs and 21 syndromic OKCs, submitted to morphological and immunohistochemical analysis of the proteins in cells of 10 fields of the epithelial component and 10 fields of the underlying fibrous capsule. We observed CXCL12 immunoexpression in epithelial cells of 20 isolated OKCs and 19 syndromic OKCs, with a statistically significant difference in the positivity index (PI) among injuries (p<0.001), with greater expression in isolated OKCs. We found CXCL12 expression in fibroblasts and endothelial cells of all isolated OKCs and in 20 syndromic OKCs, with a statistically significant difference in PI between groups (p<0.001) and greater expression in isolated OKCs. CXCR4 was expressed in cytoplasm and nucleus of suprabasal epithelial cells of all OKCs, with a statistically significant difference in nuclear PI between isolated and syndromic OKCs (p=0.007). We observed the CXCR4 cytoplasmic expression in fibroblasts and, mainly, in endothelial cells of 90.5% of the syndromic OKCs and in all isolated OKCs. We observed CXCR4 nuclear positivity in fibroblasts and endothelial cells of 20 isolated OKCs and in all syndromic OKCs. According to Spearman’s statistical test, there was a statistically significant correlation only for the epithelial syndromic OKCs between the PI of the CXCR4 cytoplasmic and nuclear expressions (r=0.730; p<0.001). In the CXCL12 and CXCR4 expression in cystic capsule, we noted a statistically significant correlation between nuclear and cytoplasmic PI of CXCR4 in isolated (r=0.698; p> 0.001) and syndromic (r=0.826; p>0.001) OKCs. The results suggest that, in the cystic epithelial component, CXCL12 chemokine and its CXCR4 main receptor seem to play a minor role in relation to the pathogenesis and the biological behavior of OKCs. In the fibrous capsule, it is likely that the evaluated proteins may be implicated in some mechanism associated with pathogenesis and differences in the biological behavior among different types of OKCs, especially in the angiogenic events responsible for injuries.