DAPK-1 as a Potential Early Marker for Malignant Transformation Risk of Oral Lichen Planus.

Introduction Oral lichen planus (OLP) comprises a chronic inflammatory autoimmune disease observed in the oral cavity. It most commonly manifests as white papules arranged confluently, drawing a picture of white lines in the form of a network (reticular form). It may emerge in other forms as well. In our study, the erosive form presents the most clinical interest. Among the biomarkers that participate in the tumorigenesis process, DAPK-1 seems promising, rendering its study necessary. This study focuses on the investigation of the presence of the DAPK-1 using immunohistochemistry in OLP compared to oral squamous cell carcinoma (OSCC), oral leukoplakia (OL), a well-established oral potentially malignant disorder, and normal oral epithelium to evaluate its possible role as an early predictor of the possibility of malignant transformation risk of OLP lesions. Methods To monitor the expression profile of the tumor suppressor protein DAPK-1, an immunohistochemical detection took place in 18 samples of OLP (reticular and erosive type), in 22 OSCC samples of all degrees of differentiation, in 30 OL samples of all degrees of dysplasia, and five normal tissue samples used as the control group. To complete the above procedure, immunohistochemistry was used in a semiquantative manner. The paraffin-embedded tissue samples were selected from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, from biopsies performed in this department as well as from St. Lukas Hospital of Thessaloniki, Greece, between 2014 and 2019. The study was conducted per the Research and Ethics Committee guidelines of Aristotle University, School of Dentistry, and the Helsinki II declaration (protocol number 29/21.11.2018).  Results The statistical analysis showed that there was no statistically significant difference in DAPK-1 staining between normal tissues and OLP (p=0.588, independent-samples Kruskal-Wallis test). On the other hand, there was a statistically significant difference between OSCCs and OLPs (p<0,001, independent-samples Kruskal-Wallis test), with the extent of expression of DAPK-1 being greater in OLP than in OSCC. In addition, there was a statistical difference in DAPK-1 expression between OLPs and OLs (p=0,001, independent-samples Kruskal-Wallis test), with DAPK-1 being expressed more in OLP than in OL. Conclusion The DAPK-1, as a pro-inflammatory with its role as a tumor suppressor factor, was highly expressed in OLP, both reticular and erosive. The relatively milder expression of DAPK-1 in OL means that, between the two disorders, OLP is less likely to progress to oral cancer. On the other hand, OLP could also offer the background for further investigation of a possible correlation between methylation (immunohistochemical expression of proteins, deriving from potentially DNA-methylated genes) and the development of inflammation. It appears that DNA methylation is important in the regulation of inflammatory genes. Conversely, inflammation may regulate the DNA methylation of many genes involved in carcinogenesis and thus should be taken into account when studying the methylation behavior of genes such as DAPK-1 in pathologies characterized by a sparse inflammatory infiltrate.
Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of the School of Dentistry, Aristotle University of Thessaloniki issued approval 29/21.11.2018. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
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