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Background: Odontogenic keratocysts constitute 10%–20% of odontogenic cysts and exhibit a distinctive corrugated parakeratinized lining epithelium. Considering that cornified envelope formation is an important phenomenon during keratinocyte differentiation, this study aimed to clarify the characteristics of cornified envelope formation in odontogenic keratocysts. Methods: We investigated the cellular distribution of cornified envelope‐related proteins (transglutaminases and their substrates), as well as the upstream regulatory protein c‐Fos, by immunohistochemical analysis of the lining epithelium of 20 odontogenic keratocysts. We examined the corresponding mRNA levels by quantitative polymerase chain reaction. Ten dentigerous cysts served as control non‐keratinized cysts. Results: The distributions of transglutaminase and their substrates except loricrin and small protein‐rich protein 1a significantly differed between odontogenic keratocysts and dentigerous cysts. There was no significant difference in c‐Fos expression between odontogenic keratocysts and dentigerous cysts. The mRNA levels of transglutaminases and their substrates were significantly higher in odontogenic keratocysts than in dentigerous cysts. However, c‐Fos mRNA levels did not significantly differ between groups. Conclusion: Surprisingly, the overall appearance of cornified envelope‐related proteins of odontogenic keratocysts was consistent with the characteristics of non‐keratinized oral mucosa identified in previous studies. These findings indicate that the contribution of cornified envelope‐related molecules in odontogenic keratocysts is similar to that in non‐keratinized oral epithelium, rather than keratinized oral epithelium, suggesting that odontogenic keratocysts are not genuine keratinized cysts. The upregulation of cornified envelope‐related genes in odontogenic epithelium could be an important pathognomonic event during odontogenic keratocyst development. [ABSTRACT FROM AUTHOR]

Cornified envelope formation is crucial for the final differentiation of keratinized epithelium. However, the mechanisms of cornified envelope formation in the oral epithelium remain unclear. The aim of this study was to clarify the differences in the distribution and expression of cornified envelope related proteins and genes between keratinized and non‐keratinized oral epithelia. We immunohistochemically investigated the distribution patterns of transglutaminase 1 (TG1), transglutaminase 3 (TG3), and their substrate proteins involucrin (IVL), loricrin (LOR), and small proline rich proteins (SPRs), in 19 keratinized and 14 non‐keratinized oral epithelium samples. TG1 and TG3 mRNA levels were investigated in both types of epithelium by real time reverse transcription polymerase chain reaction (RT‐PCR) using paraffin‐embedded specimens. Data were analyzed to identify factors involved in cornified envelope formation. We demonstrate that 11 localization patterns show statistically significant differences between keratinized and non‐keratinized oral epithelia. These factors clearly drove the separation of the two groups during cluster analysis. TG1 mRNA levels in keratinized oral epithelium were significantly higher than those in non‐keratinized oral epithelium. In conclusion, the characteristic distribution of transglutaminases and their substrates and the mRNA levels of TG1 can regulate cornified envelope formation in keratinized oral epithelium, together with the contribution of TG3 first reported in this paper. [ABSTRACT FROM AUTHOR]