Epithelial expression of SHH signaling pathway in odontogenic tumors

Abstract

Sonic hedgehog (SHH) signaling pathway plays a critical role in tooth development. Recent studies indicate that SHH signaling pathway activation occurs both in the odontogenic cyst and ameloblastoma. However, the association of SHH pathway with other subtypes of odontogenic tumor is not well documented. The objective of this paper is to investigate the protein distribution of SHH and its receptor PTC, SMO and transcription factor GLI1 in various odontogenic tumors. Odontogenic tumor tissues including 34 epithelial derived, 24 epithelial-mesenchymal derived, and 26 mesenchymal derived were examined by immunohistochemistry for SHH, PTC, SMO and GLI1. Immunoreactivity for SHH, PTC, SMO and GLI1 was detected in both epithelial derived odontogenic tumors and epithelial-mesenchymal derived odontogenic tumors with or without dental hard tissue formation. Mesenchymal derived odontogenic tumors showed no positive staining except for the focal epithelial cells in island or cord forms within the central portion of the tumor. The protein expression of SHH signaling pathway in malignant odontogenic tumors was no stronger than that in benign tumors. Each of the genes in the pathway was expressed in similar patterns in the same tumor subtype. SHH, PTC, SMO and GLI1 were detected more in the cytoplasm of the epithelial cells than in stromal cells. Immunoreactivity for GLI1 was also detected in the base membrane of the tumor cells. The findings suggest SHH, PTC, SMO and GLI1 protein are predominantly located in epithelial components in various odontogenic tumors and might participate in the proliferation of epithelial components of odontogenic tumors.