Immunohistochemical analysis of SHH, SMO and GLI-1 proteins in epithelial odontogenic lesions

Abstract The present study analyzed the expression of proteins involved in the sonic hedgehog signaling pathway (SHH, SMO, and GLI-1) in benign epithelial odontogenic lesions (odontogenic keratocyst - OKC, ameloblastoma - AB, and adenomatoid odontogenic tumor - AOT) in order to identify the role of these proteins in the pathogenesis of these lesions. The sample consisted of 20 OKCs, 20 ABs, and 10 AOTs. The Kruskal-Wallis, Mann-Whitney U, and Spearman’s (r) tests were used for statistical analysis, with the level of significance set at 5% (p < 0.05). The membrane/cytoplasmic expression of SHH was significantly higher in AB compared to AOT (p = 0.022) and OKC (p = 0.02). No differences were found in the membrane/cytoplasmic expression of SMO between the lesions studied. Regarding GLI-1, significant differences were observed at the nuclear level for AB and OKC compared to AOT (p < 0.0001). In addition, significant positive correlations were found between cytoplasmic and nuclear GLI-1 in AB (r = 0.482; p = 0.031) and OKC (r = 0.865; p < 0.0001), and between membrane/cytoplasmic SMO and cytoplasmic GLI-1 in AOT (r = 0.667; p = 0.035) and OKC (r = 0.535; p = 0.015). The results of this study confirm the participation of the sonic hedgehog signaling pathway in the pathogenesis of the lesions studied. Overexpression of SHH in ABs and nuclear expression of GLI-1 in ABs and OKCs indicate that these proteins contribute to the more aggressive behavior of these two lesions when compared to AOT.

摘要 本研究针对牙源性良性上皮病变（包括牙源性角化囊肿（odontogenic keratocyst, OKC）、成釉细胞瘤（ameloblastoma, AB）及牙源性腺瘤样瘤（adenomatoid odontogenic tumor, AOT)）中参与音猬因子信号通路（sonic hedgehog signaling pathway）的蛋白（SHH、SMO及GLI-1）的表达情况进行分析，以期明确这些蛋白在上述病变发病机制中的作用。本研究纳入的样本包含20例OKC、20例AB及10例AOT。采用克鲁斯卡尔-沃利斯（Kruskal-Wallis）检验、曼-惠特尼U（Mann-Whitney U）检验及斯皮尔曼（Spearman’s (r)）相关分析进行统计学分析，设定显著性水准为5%（p<0.05）。与AOT及OKC相比，AB中SHH的膜/胞质表达水平显著更高（p=0.022、p=0.02）。各病变组间SMO的膜/胞质表达无显著差异。针对GLI-1，AB与OKC的核表达水平均显著高于AOT（p<0.0001）。此外，在AB（r=0.482；p=0.031）及OKC（r=0.865；p<0.0001）中，胞质与核GLI-1表达呈显著正相关；在AOT（r=0.667；p=0.035）及OKC（r=0.535；p=0.015）中，SMO的膜/胞质表达与胞质GLI-1表达呈显著正相关。本研究结果证实，音猬因子信号通路参与了上述病变的发病机制。与AOT相比，AB中SHH的过表达以及AB与OKC中GLI-1的核表达，表明这些蛋白可促使这两种病变表现出更强的侵袭性生物学行为。