# Immunohistochemical Expression of DAPK-1 in Oral Leukoplakia And Oral Squamous Cell Carcinoma: A Preliminary Study

## TL;DR

This study examines DAPK-1 protein levels in oral leukoplakia and oral cancer, finding lower levels in more severe cases, suggesting it may act as a tumor suppressor.

## Contribution

The study presents preliminary evidence that DAPK-1 expression decreases with increasing severity of oral lesions, potentially serving as a biomarker for malignancy.

## Key findings

- DAPK-1 expression was higher in oral leukoplakia without dysplasia compared to those with moderate/severe dysplasia.
- DAPK-1 expression was significantly lower in oral squamous cell carcinoma compared to mild dysplasia cases.
- Reduced DAPK-1 staining may indicate aggressive cancer behavior and potential malignant transformation.

## Abstract

Introduction: The silencing of death-associated protein kinase 1 (DAPK-1) is an effective way of inactivating a tumor-suppressing mechanism. The aim of this study was to investigate the immunohistochemical expression of DAPK-1 in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC).

Methods: The immunohistochemical (IHC) detection of DAPK-1 was carried out in cases of OLs and OSCCs. DAPK-1 molecules’ tissue distribution in OLs/OSCCs tissues was evaluated using semiquantitative immunohistochemistry in representative paraffin-embedded tissue samples (57 in total) from 2004-2019, retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece and the St Lukas Hospital of Thessaloniki, Greece. The inclusion criterion was the presence of sufficient precancerous or cancerous biological material (estimated as more than 70% per tissue specimen) in the paraffin cubes. The exclusion criterion was the opposite, i.e. the lack of sufficient material due to previous sections. Statistics for IHC were evaluated by a non-parametric Mann-Whitney U Test. A two-sided p-value < 0.05 was considered statistically significant.

Results: DAPK-1 IHC expression was increased in OLs without dysplasia and with OLs with mild dysplasia compared to moderate/severe dysplasia (p=0.019, Mann-Whitney U Test) and OSCCs (p=0.003, Mann-Whitney U Test).

Conclusions: DAPK-1 seemed to function as an oncosuppressor molecular biomarker, as its expression was decreased in areas of cellular dysplasia in OLs and in areas of OSCCs composed of less differentiated cells. The clinical application of this biomarker is that the positively stained, potentially malignant lesions are less likely to transition into malignancy, and cancerous lesions are more likely to behave non-aggressively. On the other hand, the lack of staining could signify the loss of this oncosuppressing ability, and it could be a potential prognostic biomarker for OSCC’s aggressive biologic behavior if considered with other clinical parameters and a prognostic factor of malignant transformation of potentially malignant lesions. Since this is a preliminary study, more studies with larger sample sizes are required to support these conclusions.