Objectives Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis de novo, as well as through the transformation of oral potential malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of our study was to detect the expression of stemness-type CSC marker CD147 in oral leukoplakias (OLs), the most common OPMD, and OSCCs as well. Materials and methods This study focuses on the semiquantitative immunohistochemical pattern of the expression of the CSC protein biomarker CD147 in paraffin-embedded samples of 20 OSCCs of different grades of differentiation and 30 cases of OLs without or with different grades of dysplasia, compared to the normal oral epithelium in terms of cells’ stain positivity. Statistical analysis was performed through Statistical Package for Social Sciences (SPSS) version 25.0 (IBM SPSS Statistics, Armonk, NY) with Pearson chi-square test, and the significance level was set at 0.05 (p=0.05). In addition, the study clarified the expression of the respective gene of CD147 through quantitative polymerase chain (qPCR), in paraffin-embedded samples of the two extreme graduations: OLs of mildly dysplastic or non-dysplastic cases (n=10 cases) and OSCCs of moderately/poorly differentiated cases (n=17). Statistical analysis was then performed through SPSS version 25.0 with an independent paired t-test, and the significance level was set at 0.05 (p=0.05). Results The gene CD147 was expressed in all cases, although no statistically significant correlations were established. Regarding its protein products, the characteristic membranous staining of CD147 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. CD147 was upregulated significantly in the moderately and severely dysplastic OLs than in the mildly dysplastic and non-dysplastic OLs (p=0.008). Also, CD147 was upregulated significantly in the mildly dysplastic and non-dysplastic OLs than in the normal oral epithelium (p=0.012). Discussion The characteristic expression of CD147 in OLs and OSCCs’ lesions suggests the presence of stemlike cancer cells, illustrating an underlying effect on the early stages of oral dysplasia, in the OL stage. The clinical application of CD147 as prognostic factor requires the experimental evaluation in larger number of samples. Conclusion Stem cells play an important role in the process of carcinogenesis. A major goal in cancer research is the identification of specific biomarkers for the detection of cancer stem cells. CD147 is considered as an innovative stem cell marker. Our findings in oral mucosal potentially malignant disorders showed that CD147 is expressed more intensely in parallel with the progression of the grade of dysplasia in OL. On the other hand, in oral squamous cell carcinoma, CD147 expression remains stable regardless of the degree of differentiation.

Introduction: Cancer stem cells (CSCs) are incriminated for initiating the process of carcinogenesis either de novo or through the transformation of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of this study was to detect the expression of embryonic-type CSC markers OCT3/4 and SOX2 in OSCCs and oral leukoplakias (OLs), the most common of OPMDs. Materials and methods: The study type is experimental, and the study design is characterized as semiquantitative research, which belongs to the branch of experimental research. The experiment was conducted in the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. This study focuses on the semiquantitative immunohistochemical (IHC) pattern of expression of CSCs protein-biomarkers SOX2 and OCT3/4, in paraffin embedded samples of 21 OSCCs of different grades of differentiation and 30 cases of OLs with different grades of dysplasia, compared to five cases of normal oral mucosa in both terms of cells’ stain positivity and intensity. Statistical analysis was performed through SPSS 2017 Pearson Chi-square and the significance level was set at 0.05 (p=0.05). The expression of the respective genes of SOX2 and OCT3/4 was studied through quantitative polymerase chain reaction (qPCR), in paraffin-embedded samples of 12 cases of OLs with mild/non dysplasia and 19 cases moderately/poorly differentiated OSCCs(n=19) and five normal mucosa using the Independent Paired T-test. Results: The genes SOX2 and Oct3/4 were expressed in all examined cases although no statistically significant correlations among normal, OL and OSCC, were established. A nuclear/membrane staining of OCT3/4 was noticed only in three out of 21 OSCCs but in none of OLs or normal cases (without statistical significance). A characteristic nuclear staining of SOX2 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. SOX2 was significantly detected in the OSCCs group (strong positivity in 17/21) than in the OL group (30 cases, mostly mildly stained) (p-value=0.007), and the normal oral epithelium (mild stained, p=0.065). Furthermore, SOX2 was overexpressed in well differentiated OSCCs group (5/OSCCs, strongly stained) rather than in mildly dysplastic and non-dysplastic OLs samples (14/OLs, mildly stained) (p-value =0.035). Conclusion:The characteristic expression of SOX2 but not of OCT3/4 in OLs' and OSCCs’ lesions suggests the presence of neoplastic cells with certain CSC characteristics whose implication in the early stages of oral tumorigenesis could be further evaluated. The clinical use of SOX2, as prognostic factor, requires further experimental evaluation in larger number of samples.

Background/Objectives: Salivary adenoid cystic carcinoma (ACC) is a rare but aggressive neoplasm that predominantly arises from the salivary glands, accounting for a significant proportion of salivary gland cancers. The aim of this literature review is to illustrate the current insights on ACC with regards to related genes and molecular pathways by analyzing original research articles from the period 2015–2025. Methods: An electronic search of literature was performed between January and February 2025 to identify all articles investigating the current insights on salivary gland adenoid cystic carcinoma and its related genes and molecular pathways. The search was conducted using MEDLINE (National Library of Medicine)-PubMed with restrictions concerning the date of publication. In particular, we focused on the period 2015–2025 using the following keywords: Salivary gland adenoid cystic carcinoma AND genes AND molecular pathways. This was followed by a manual search, and references were used to identify relevant articles. Results: In total, 41 articles were identified through the keywords. After the implementation of the time frame 2015–2025, 31 articles remained. Subsequently, by reading the titles and abstracts and thereby excluding non-original research articles and articles written in a language other than English, 23 articles remained. Conclusions: These studies identified 23 relevant genes or pathways whose analysis yielded the most recent data regarding their function. The classification of ACC is multifaceted, encompassing distinct histological subtypes that are crucial for determining prognosis and treatment approaches. Current oncological practices classify ACC based on these histological features alongside emerging genetic and molecular markers that promise to enhance our understanding of the disease’s biology. Diagnostic strategies have evolved, leveraging techniques such as biopsy and molecular diagnostics, which have significantly improved the detection and characterization of ACC. Regarding treatment, the management of ACC remains a challenge due to its propensity for local invasion and metastasis, with surgery, radiation, and chemotherapy being the mainstays of therapy. The development of targeted therapies based on ACC’s molecular profile will allow for a better prognosis and an enhanced quality of life of patients.

Introduction: Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis by enabling the self-renewal and self-proliferation of the cancer cells. This study aimed to investigate the presence of epithelial cells with cancer stem cells characteristics (ALDH+) in the early stages of oral precancerous lesions (Oral Leukoplakias) and the frequency of these cells in the different stages of oral squamous cell carcinomas (OSCCs). Materials & methods: The aim of this study was the detection of the immunohistochemical pattern of expression of CSC protein-biomarker ALDH1&2 (sc-166362, Santa Cruz Co, Dallas, Texas, USA) in paraffin-embedded samples of 30 cases of leukoplakia of all degrees of dysplasia and 21 cases of oral squamous cell carcinomas (OSCC) of all degrees of differentiation compared to the histologically normal oral epithelium. The samples were retrieved from 2009-2019 from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. The samples were evaluated through a three-tier scale (positive cells Ι: 6-35%, ΙΙ: 36-70%, ΙΙΙ: 71-100%). Statistical analysis was performed through SPSS Pearson Chi-square, and the significance level was set at 0.05 (p=0.05). Results: The staining of ALDH1&2 was observed mildly in the cell membrane of cells in the stratum spinosum of the normal epithelium and the cell membrane of cells in the stratum basale of the normal epithelium, characteristically at the interface point with the basal membrane. ALDH1&2 were expressed significantly more in the OSCC than in the leukoplakia (p-value=0.0001) and the normal epithelium (p-value=0.0001). Mainly, ALDH1&2 were expressed significantly more in the severely and moderately dysplastic oral leukoplakia compared to the mildly dysplastic and non-dysplastic leukoplakia (p-value=0.001). Discussion: The characteristic expression of ALDH in potentially malignant oral and OSCC lesions suggests the presence of CSCs and their possible implication in the early stages of oral tumorigenesis, even at the stage of oral leukoplakia.

Head and neck squamous cell carcinoma (HNSCC) belongs to the most frequent cancer subtypes in the world. Mutations due to genetic and chromosomal instability, syndromes such as Fanconi anemia and the Bloom syndrome, environmental risk factors such as tobacco smoking, alcohol and human papillomavirus infection (HPV) subtypes 16,18,31,33,35,52,58 are implicated in its pathogenesis. The HNSCC belongs to the solid tumors of epithelial origin and consists of stromal, inflammatory, cancer cells and most importantly a fraction of them, the cancer stem cells (CSCs). The identification of the CSCs through their biomarkers such as CD44, CD10, CD166, CD133, CD271, ALDH, Oct4, Nanog, Sox2 and Bmi1, the maintenance of their subpopulation through epithelial to mesenchymal transition, the role of HPV infection regarding their prognosis and of their microenvironment regarding their resistance to therapy, all constitute key elements that must be taken thoroughly into consideration in order to develop an effective targeted therapy. There are already therapies in place targeting specific related biomarkers, important biochemical pathways and growth factors. The aim of this literature review is to illustrate the treatment modalities available against the cancer stem cells of head and neck squamous cell carcinoma.