Immunohistochemical analysis of SHH, SMO and GLI-1 proteins in benign lesions of the odontogenic epithelium
Odontogenic cysts. odontogenic tumors. Hedgehog proteins. immunohistochemistry.
The odontogenic cysts and tumors represent heterogeneous groups of lesions that affect the gnatic bones and which have not yet fully clarified pathogenesis. Therefore, several studies have been developed in order to analyze if deregulation in some signaling pathways would be related to the development and progression of these lesions. Among the studied pathways, we highlight the Sonic Hedgehog pathway, which plays an important role in the embryonic development of the dental organ and is mutated in some cancers. The aim of the present study was to analyze and compare the immunohistochemical expression of proteins involved in the Sonic Hedgehog signaling pathway (SHH, SMO and GLI-1) in odontogenic keratocysts (OK), ameloblastomas (AMB) and adenomatoid odontogenic tumors (AOT). Protein immunoexpression was semi-quantitatively evaluated in each case studied and the data were subjected to statistical analysis using the Kruskal-Wallis (KW), Mann-Whitney (U) and Spearman (r) tests, with the significance level set at 5% (p <0.05). When analyzing SHH protein in the three lesions, it was observed that AMB showed significantly higher membrane/ cytoplasmic expression compared to AOT and OK. Regarding the membrane/cytoplasmic analysis of the SMO, no differences were identified between the lesions studied. For GLI-1 protein, statistically significant differences were found at nuclear level for AMB and OK compared to AOT. In addition, positive correlations with statistical significance were observed between cytoplasmic GLI-1 and nuclear GLI-1 for AMB and OK, and between membrane/cytoplasmic SMO and cytoplasmic GLI-1 for AOT and OK. The results of the present study confirm the participation of this signaling pathway in the pathogenesis of the lesions studied and the overexpression of SHH in AMBs and nuclear GLI-1 in AMBs and OKs, indicating that these proteins contribute to the more aggressive biological behavior of these two lesions when compared to AOT.