Alterations in intercellular and cell-extracellular matrix connections contribute to tumour development. This study investigates the expression of specific cell adhesion molecules (CAMs) in salivary gland tumors (SGTs). Formalin–fixed, paraffin– embedded tissue specimens of different types of 34 benign and 31 malignant SGTs and normal salivary glands were studied using Envision/HRP immunohistochemical technique for Desmoglein-2 (Dsg-2), beta4-integrin, CD44s and ICAM-1. Intensity of staining was evaluated in a semi-quantitative manner. Results were analyzed using Kendall’s τ and Spearman’s ρ as correlation criteria. Dsg-2 in intercellular space, beta4-integrin in cell-basal membrane, and CD44s in both types of contacts were strongly expressed in normal acinar and ductal cells, whereas ICAM-1 was expressed only at the endothelium and sparse stromal cells and monocytes. Strong correlation was found between Dsg-2 expression in adenomas and controls and between adenocarcinomas and controls. In adenomas, a distinct cytoplasmic presence of Dsg-2 was observed in addition to the usual membranous expression, with decreased expression in comparison with normal tissue. In malignant SGTs, Dsg-2 expression was absent. In most SGTs, beta4-integrin was expressed also with a distinct pattern, involving the cytoplasm and the unpolarised membrane, while CD44 was found only on the membrane. Strong correlation between beta4-integrin expression in adenomas and controls was noted, while CD44 expression was found to be correlated significantly between adenocarcinomas and controls (p < 0.001). Regarding ICAM-1, its expression was found increased in adenomas, with non-specific distribution in malignant SGTs and strong correlation between the histological subtypes and controls (p < 0.001). The different expression profile of CAMs in SGTs could possibly suggest a role on their pathogenesis, representing a model of how neoplastic cells can take advantage of normal tissue architecture and cell-extracellular matrix interactions.

Background/Objectives: DAPK-1 plays a crucial role among molecules that may be affected by DNA hypermethylation. The aim of this study is to investigate the DNA methylation of DAPK-1 gene in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) compared to normal oral epithelium and to evaluate the possible role of methylated DAPK-1 as an indicator of the early onset of malignant transformation of oral potentially malignant disorders. Methods: The paraffin embedded tissue samples were retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece and St Lukas Hospital of Thessaloniki, Greece during the period of 2014–2019. The tissue samples included 83 OPMDs samples, 39 OSCC samples and 12 samples of normal oral epithelium. The PCR process followed, targeting four different DAPK-1 gene primers. Results: Regarding OSCC, it was found that all 39 OSCCs samples were methylated in DAPK-1 promoter region, whereas only 2 out of 12 normal tissues samples showed DAPK-1 promoter hypermethylation (p < 0.001 Fisher’s exact test). A total of 17 out of 83 OPMDs were DAPK-1 methylated (five erosive oral lichen planus samples, three non-dysplastic oral leukoplakias, eight mildly dysplastic oral leukoplakias and one sample belonging to the group of moderately and severely dysplastic oral leukoplakia). Conclusions: Since epigenetic changes occur early in carcinogenesis and are potentially reversible, they could be used as disease biomarkers for diagnosis, prognosis and prediction, as well as therapeutic targets. DAPK-1 methylation is mostly present in the early stages of dysplasia as well as in all cases of oral cancer.

Background/Objectives: Ameloblastoma is a benign odontogenic neoplasm characterized by locally aggressive behavior and frequent recurrences despite surgical treatment. It originates from odontogenic epithelium, including the cell rests of the dental lamina, remnants of the enamel organ, epithelial cell rests of Malassez, or the basal cell layer of the oral mucosa. Investigation of the etiopathogenesis of ameloblastoma has gained critical relevance due to the need for extensive surgical procedures, high recurrence rates, and its malignant potential. Accordingly, the aim of the present narrative review is to summarize current evidence regarding key aspects of ameloblastoma etiopathogenesis, with emphasis on signaling pathways, mutations, epigenetics, and epithelial–stromal interactions. Methods: An extensive literature search was conducted using the PubMed, Scopus, and Google Scholar databases, employing the keywords: “etiology”, “pathogenesis”, “molecular”, “biomarkers”, “cellular”, “epigenetic”, “mutation”, “pathway”, and “ameloblastoma”. In vitro studies, clinical studies, case reports, and narrative and systematic reviews published in English were included, without restriction on publication year. Results: Current evidence indicates that ameloblastoma pathogenesis is driven by dysregulation of multiple signaling pathways, particularly the MAPK and Sonic Hedgehog pathways, through recurrent activating BRAF and SMO mutations. In addition, alterations affecting the WNT/β-Catenin and PI3K/AKT signaling cascades, epigenetic modifications, and epithelial–stromal interactions, contribute to tumor behavior. Conclusions: Despite significant advances, genotype–phenotype correlations, mutation frequencies and coexistence, clonality, and other associations remain incompletely understood. Larger tumor cohorts and robust meta-analyses are required to clarify these associations and to leverage the development of personalized therapeutic strategies.