Journal of Oral Pathology & Medicine最新文献

Background: Hereditary gingival fibromatosis (HGF) is a rare, genetically heterogeneous disorder characterized by benign, slowly progressive fibrous overgrowth of the gingiva. This study aimed to identify the pathogenic genes responsible for non-syndromic HGF and to elucidate the activation mechanism for truncated SOS1 protein.

Methods: Genomic DNA was extracted from peripheral blood samples of two unrelated Han Chinese families with non-syndromic HGF. Whole-genome sequencing (WGS) was utilized to identify pathogenic mutations. Bioinformatic analyses were conducted to predict the deleteriousness of the identified mutations. The phenotypic spectrum of SOS1 mutations was summarized by literature review methods, with a particular focus on the gingival hyperplasia phenotype. Genotype-phenotype correlations were analyzed.

Results: WGS identified two novel SOS1 mutations, c.3262dupA/p.Thr1088fs and c.1523A>G/p.Asn508Ser in two unrelated Han Chinese families with non-syndromic HGF. MutationTaster and CADD revealed the c.1523A>G/p.Asn508Ser mutation as disease-causing. The mutational spectrum of SOS1 showed a predominance of missense mutations, among which three were linked to the gingival hyperplasia phenotype. Frameshift mutations in the C-terminal region of SOS1 were all associated with the gingival hyperplasia phenotype. A novel "Dual-Gated Model" was introduced to elucidate the activation mechanisms for both the normal and truncated forms of SOS1.

Conclusions: Our study identified two novel SOS1 mutations, c.3262dupA/p.Thr1088fs and c.1523A>G/p.Asn508Ser, in two unrelated Han Chinese families with non-syndromic HGF. A novel "Dual-Gated Model" was proposed to elucidate the full activation process of wild-type and truncated SOS1. We extended the mutational spectrum of SOS1 in non-syndromic HGF and provided new insights on the molecular mechanism of pathogenesis.

Introduction: Dysregulated expression of urokinase-type plasminogen activator (PLAU), a serine protease, is frequently associated with various cancers. However, in oral squamous cell carcinoma (OSCC), the specific biological functions and mechanisms of action of PLAU remain unclear.

Methods: Western blot (WB) analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of PLAU in oral squamous cell carcinoma; Flow cytometry was used to assess changes in OSCC cell cycle and apoptosis following PLAU knockdown. Transwell assays were conducted to evaluate alterations in cell invasion and migration after PLAU knockdown. LinkedOmics database was employed to analyze the correlation between PLAU and TGF-β1.

Results: Our study using GEPIA2 dataset analysis and WB experiments revealed that PLAU expression was upregulated in HNSC tissues and OSCC cell lines and was significantly associated with overall survival in patients. Furthermore, the invasive and migratory abilities of UM1 cells were significantly reduced following PLAU knockdown, as demonstrated by scratch assays and Transwell migration assays. Subsequently, Western blot analysis revealed that PLAU knockdown effectively inhibited the epithelial-mesenchymal transition (EMT) process. Meanwhile, LinkedOmics database analysis revealed a significant positive correlation between TGF-β1 and PLAU. Further investigations demonstrated that TGF-β1 induces PLAU upregulation, which subsequently promotes the migration, invasion, and EMT process in OSCC cells. Conversely, PLAU knockdown abrogates these TGF-β1-mediated effects.

Conclusion: PLAU acts as a key oncogenic driver in OSCC and may serve as a potential diagnostic and prognostic biomarker. More importantly, the TGF-β1-PLAU axis may offer new therapeutic targets for OSCC treatment.

Introduction: Chronic hyperplastic candidiasis (CHC) has a controversial potential role in the carcinogenesis of oral epithelium. In addition, histological overlap between CHC and atypical epithelial proliferation with Candida (AEPC) may cause a diagnostic dilemma. In this pilot study, potential premalignant markers including tumor suppressor gene proteins p53 and p16, and cancer stem cell markers CD44 and OCT4, were investigated in CHC and AEPC with benign and malignant validation groups.

Materials and methods: A total of 20 tongue lesions were identified, with 5 cases of each: benign validation group of traumatic fibroma, CHC without dysplasia, AEPC, and malignant validation group of moderately differentiated squamous cell carcinoma (SCCA). IHC staining was performed with p53, p16, CD44, and OCT4. Inter-observer variability between two pathologists' independent scores was determined using Cohen's kappa (k). A third pathologist served as tiebreaker for disagreement. Chi-square testing was performed between diagnostic groups and staining results.

Results: Overall agreement of staining for all stains was good (κ = 0.614) for intensity, moderate (κ = 0.544) for percentage, and good (κ = 0.612) for p53 wild or atypical pattern analysis (based on prior studies). p53 and CD44 staining showed statistically significant differences between the fibroma/CHC cases and the AEPC/SCCA cases. The most diagnostic measures were p53 pattern, which categorized 100% of fibroma/CHC cases as wild type and 90% of AEPC/SCCA groups as atypical (p < 0.001), and CD44 staining above 50%, which diagnosed 70% of AEPC/SCCA cases versus 0% of fibroma/CHC cases (p = 0.004). Using these two together, all AEPC/SCCA cases were diagnosed. p16 and OCT4 were not significant in differentiating between diagnoses in this study.

Conclusions: In this pilot study, p53 pattern and CD44 percentage showed significant potential to serve as useful diagnostic aids. Future studies with larger sample sizes are necessary to validate these findings and explore the potential of these markers in determining the transformation risk of CHC and AEPC.

Background: Human papillomavirus (HPV)-16 is the most commonly found HPV-type in HPV-induced oropharyngeal squamous cell carcinomas (OPSCC). The serological response to HPV oncoproteins could be a way to detect HPV-driven OPSCC early. A rapid test for the detection of HPV16 L1 antibodies in blood was developed in 2015 (PrevoCheck).

Methods: Prospectively, we included 42 patients with newly diagnosed head and neck squamous cell carcinomas (HNSCC). Pretreatment venous blood samples were collected and analyzed with PrevoCheck. The results were interpreted by 2 reviewers. Immunohistochemistry with p16 and HPV DNA-PCR testing served as a reference standard.

Results: Sixteen patients had HPV-positive tumors (38.1%). PrevoCheck showed 2 true positives, 26 true negatives, 0 false positives, and 14 false negatives, which resulted in a sensitivity of 12.5% (95% CI: 1.6%-38.4%) at a specificity of 100% (95% CI: 86.8-100). Interobserver agreement showed perfect agreement.

Conclusion: A negative result in a test with a high sensitivity can be used to rule out disease, that is, HPV16-related HNSCC. We found 14 false negative results, resulting in low sensitivity for PrevoCheck. This test does not seem suitable to screen for HPV16-related head and neck cancers.

Background: Cervical lymph node metastasis is one of the most important prognosticators in oral squamous cell carcinoma (OSCC). The presence of extranodal extension (ENE) in metastatic nodes further worsens the prognosis. The primary objective of this study was to develop a simple model to predict ENE in OSCC using demographic and clinicopathological parameters that are easily available in a preoperative clinical setting.

Methods: All patients who underwent surgery for the treatment of primary OSCC of the tongue or buccal mucosa with neck dissection (ND) between 1998 and 2020 from two oral pathology diagnostic units were included in the study. Chi-square tests were utilised to analyse the presence/absence of associations between each input parameter and ENE. The strengths of these associations were assessed using univariable and multivariable logistic regressions and indicated as odds ratios.

Results: Among the 1098 OSCC patients included in the study, 185 (16.85%) patients exhibited ENE. In the multivariable logistic regression model the odds for ENE were greater in females and tongue OSCC. Similarly, increasing T category and DOI as well as a dyscohesive WPOI were associated with a greater odds ratio for ENE. The AUCs from the 10-fold cross-validations to assess the predictive ability of the newly developed model ranged from 0.655 to 0.842 with a 95% CI of 0.663-0.744, indicating that the diagnostic accuracy of our model was acceptable.

Conclusion: Our model confirms that a higher risk of ENE is associated with female gender, tumours of the tongue, increasing tumour size as well as DOI and a dyscohesive WPOI.

Objective: Acyclovir-resistant herpes simplex virus infections pose a significant challenge in immunosuppressed patients. This study aimed to characterize the clinical features, treatment outcomes, and mortality associated with acyclovir-resistant herpes simplex virus infection.

Materials and methods: A retrospective analysis was conducted on 18 patients diagnosed with acyclovir-resistant herpes simplex virus. Diagnosis was confirmed via plaque reduction assay. Data on demographics, underlying conditions, oral and systemic manifestations, management, and outcomes were retrieved and analyzed.

Results: The cohort was comprised of 10 women and eight men with a median age of 41.5 years. Acute myeloid leukemia was the most common underlying medical condition (n = 5), and 17 patients had undergone allogeneic hematopoietic cell transplantation. Oral lesions were observed in all 18 cases, primarily on the tongue (n = 12) and lips (n = 11). Acyclovir resistance was detected after a median of 151.5 days (range: 30-1736 days), after which foscarnet became the primary treatment. Despite therapy, 11 patients died after a median survival of 3 months post-diagnosis.

Conclusions: Acyclovir-resistant herpes simplex virus infections are associated with considerable morbidity and mortality in immunocompromised patients. These findings highlight the need for heightened awareness, alternative antiviral therapies, and improved prophylactic strategies to manage these patients more effectively.

Clinical relevance: Dentists play a key role in detecting acyclovir resistance through persistent oral HSV lesions, emphasizing early recognition, referral, and supportive care.

Background: Oral leukoplakia (OL) is a potentially malignant disorder of the oral mucosa. Accurate prediction of malignant transformation (MT) remains a clinical challenge. This study aimed to develop and evaluate a machine learning model that integrates histopathological, demographic, and DNA content features to predict MT risk in OL.

Methods: We conducted a retrospective cohort study of 97 OL cases-18 with confirmed MT and 79 non-transformed controls-selected from a larger series. Each case included clinicopathological features, and DNA content data obtained by flow cytometry for cell cycle phases (G1, S-phase, G2 and excess DNA beyond the tetraploid region [4cER]). All cases had a minimum 5-year follow-up or histologically confirmed transformation. A multilayer perceptron (MLP) model was trained on 27 features. Stratified five-fold cross-validation and minority class oversampling (positive filling) were used to improve learning and mitigate data imbalance. Performance was evaluated using accuracy, sensitivity, specificity, F1-score, AUC, and Kaplan-Meier survival analysis.

Results: Significant predictors of MT included 4cER (p = 0.005), G2 phase (p = 0.04), dysplasia grading (p = 0.003), and inflammatory infiltrate (p = 0.01). The optimized model yielded 72% sensitivity, 96% specificity, and an AUC of 85.4%. Survival analysis showed significantly poorer outcomes in the high-risk cases predicted by the model (p < 0.0001).

Conclusion: Integrating DNA content analysis with machine learning provides an objective and clinically useful model to stratify malignant risk in OL, complementing conventional histopathology and supporting personalized patient management.

Background: Trigeminal neuralgia is a common neuropathic pain of the oral and maxillofacial region. P2X7 receptor, a neural mediator, P2X7 receptor is closely related to this condition. Despite several studies on the role of Jujuboside A in sleep, few reports are available on its effects on chronic neuropathic pain.

Methods: In this study, a rat trigeminal neuralgia model was established by chronic constriction injury of the infraorbital nerve. Rats were intervened with Jujuboside A and P2X7 shRNA. For the behavioral aspect, the changes in the facial mechanical pain withdrawal threshold of the rats were measured. Molecular biology techniques such as Western Blotting, Real-Time Quantitative PCR, Immunohistochemistry and Enzyme-Linked Immunosorbent Assay were used to determine the changes in the P2X7 receptor, pyroptosis pathway, and inflammatory factors.

Results: The facial mechanical withdrawal threshold showed a significantly greater reduction in the trigeminal neuralgia group than in the sham group at 14 days post-operation. Jujuboside A therapy could alleviate the facial allodynia and inhibit the up-regulation of P2X7 expression in the spinal trigeminal subnucleus caudalis. Additionally, the expression of P2X7, nucleotide-binding domain, leucine-rich family, and pyrin domain-containing 3 caspase-1 and interleukin-1β was significantly greater in the trigeminal neuralgia group than in the sham group, suggesting activation of the pyroptosis cascade; this could be reversed by Jujuboside A application. Moreover, Jujuboside A administration downregulated the phosphorylation of ERK1/2 in the spinal trigeminal subnucleus caudalis of the trigeminal neuralgia group. Molecular docking demonstrated a high binding force between Jujuboside A and P2X7. Furthermore, the P2X7 knockdown treatments effectively increased the facial mechanical withdrawal threshold of trigeminal neuralgia rats.

Conclusion: These findings suggest the potential benefits of Jujuboside A in trigeminal neuralgia treatment through suppression of pyroptosis by inhibition of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing 3/caspase-1 pathway mediated by the P2X7 receptor in the spinal trigeminal subnucleus caudalis.