Enhanced Expression of Hedgehog Pathway Proteins in Oral Epithelial Dysplasia

Abstract

The aim of this study was to characterize the profile of the proteins involved in the Hedgehog signaling pathway to aid in the understanding of the pathogenesis of oral epithelial dysplasia (OED). The proteins SHH, PTCH1, HHIP, SUFU, GLI1, and cyclin D1 were evaluated by immunohistochemistry in 25 cases of OED, 4 of non-neoplasic oral mucosa, 8 of inflammatory fibrous hyperplasia and 5 of hyperkeratosis. SHH proteins were predominant in OED cases. Although PTCH1 protein was observed in all cases, this molecule was more highly expressed in OED. The inhibitor protein SUFU was present in OED and HHIP protein was overexpressed in OED. GLI1 proteins were predominantly found in the nuclei of epithelial cells in OED. Basal and suprabasal cells in the epithelial lining were positive for cyclin D1 only in OED. In conclusion, comparative analysis of the proteins involved in the Hedgehog pathway suggests that enhanced expression of these proteins can play an important role in the biological behavior of OED.

Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation

“…The present results corroborate recently published findings indicating the reactivation of the Hh pathway in OSCC, which appears to participate in the pathogenesis of this disease [9][10][11]30]. Furthermore, the proteins involved in this pathway (SHH, IHH, and GLI1) were found to be overexpressed in OSCC tumors in comparison to TMs and NNMs.…”

“…Of the nine TM cases studied, five had oral epithelial dysplasia concomitant with elevated SHH, IHH, and GLI1 protein expression. Furthermore, Dias et al [30] recently demonstrated that the Hh pathway can be activated in OED, a stage precedent to carcinoma development.…”

Glypican-1, -3, -5 (GPC1, GPC3, GPC5) and Hedgehog Pathway Expression in Oral Squamous Cell Carcinoma

“…Deregulation of embryonic signaling pathways, such as the Hedgehog (HH) pathway, can result in tumor development 3–6. Reactivation of the HH pathway has been described in OSCC7–9 and its precursor lesion, oral epithelial dysplasia 10. HH pathway activity occurs in the primary cilia, a sensory organelle formed by a projection of the cellular plasma membrane composed of tubulin subunits 11,12.…”

“…[3][4][5][6] Reactivation of the HH pathway has been described in OSCC [7][8][9] and its precursor lesion, oral epithelial dysplasia. 10 HH pathway activity occurs in the primary cilia, a sensory organelle formed by a projection of the cellular plasma membrane composed of tubulin subunits. 11,12 In the absence of morphogens [sonic Hedgehog (SHH), Indian HH, or desert HH], the transmembrane receptor Patched 1 (PTCH1) is located within the primary cilium, promoting the suppression of smoothened (SMO) activity.…”