Endoplasmic Reticulum Stress-Associated Chaperones, Bip/GRP78 and Calnexin are Overexpressed in Keratocystic Odontogenic Tumours

Abstract

Objectives: Odontogenic keratocysts (OKCs) are developmental cysts that have been reclassified according World Health Organization (WHO), to keratocystic odontogenic tumours (KCOTs), a term that better reflects their neoplastic nature. The aim of present study is to evaluate the induction of stress of the endoplasmic reticulum and execution of the resulting unfolded protein response in keratinocystic odontogenic tumours. Material and Methods: We analyzed by immunohistochemistry the expression of the chaperones BiP/GRP78 and calnexin in 24 cases of KCOTs. As controls, we have used 9 cases of periapical or radicular cysts (PACs) and 5 cases of Fibromas (FBs). The PACs and the FBs were included in the analysis, as PACs are the most common type of inflammatory odontogenic cysts of and FBs, as lesions of the connective tissue with unaffected epithelium. Results: Analysis revealed a strong association between both BiP/GRP78 and calnexin expression and KCOTs: 18 out of 24 (75%) KCOTs expressed BiP/GRP78 as opposed to 1 out of 9 (13%) PACs, and none of 5 FBs evaluated (P < 0.001, x2-test). Calnexin was expressed in 11 out of 24 KCOTs (46%) but only one out of 9 (13%) PACs, and none of the 5 FBs analyzed (P < 0.001, x2-test). Conclusions: Study results imply that induction of endoplasmic reticulum stress maybe of diagnostic value in keratocystic odontogenic tumours characterization. In addition to recent findings suggesting that endoplasmic reticulum stress plays a causative role in keratinization of epithelia, pharmacological interference with the execution of the unfolded protein response should be considered for the management of keratocystic odontogenic tumours.

Keywords

• dental tissue neoplasms
• endoplasmic reticulum stress
• GRP78 protein
• molecular chaperone
• phosphoprotein pp90