Journal of Oral Pathology & Medicine最新文献

Background: Oral lichen planus (OLP) is a chronic T-cell-mediated immune disease of unknown aetiology. MicroRNA (miRNAs) are short non-coding RNAs capable of regulating mRNA and may have roles in T-cell-related diseases. The aim of this study was to investigate the profile of miRNAs in OLP patients and its interaction with potential target genes.

Methods: Total RNA was extracted from fresh frozen biopsies from 24 patients with OLP and 8 control patients. The NanoString Counter Analysis System was used to analyse total RNA samples for differential miRNA expression. NanoString expression was confirmed by RT-qPCR analysis. Genes potentially targeted by upregulated and downregulated miRNAs were identified, and RT-qPCR was employed to investigate the expression of target genes in OLP and controls. Probability values < 0.05 were considered statistically significant.

Results: NanoString analysis showed that eight miRNAs, miR-155, miR-146a, miR-3195, miR-342, miR-4516, miR-21, miR-29a and miR-193 were upregulated in OLP tissues. Contrarily, the other eight miRNAs, miR-221, miR-200b, miR-149, miR-205, miR-27b, miR-95, miR-127b, miR-95, miR-206 were downregulated in OLP tissues. NanoString findings have been confirmed by RT-qPCR results for four upregulated miRNAs, miR-155, miR-146a, miR-29a and miR-342, and one downregulated miRNA, namely miR-205. The expression of two target genes, namely MYC for miR-29a and interleukin-24 (IL-24) for miR-205, was found to negatively correlate with the respective miRNA. This suggests that MYC and IL-24 could be regulated by the above miRNAs in OLP.

Conclusions: The work presented in this study suggests that miRNAs could be involved in both the immunopathogenesis and malignant transformation of OLP.

Introduction: Methylation of tumor-suppressor gene promoters, particularly p16^INK4A, is implicated in oral carcinogenesis. Although associations with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) have been reported, no systematic review has examined these conditions while assessing evidence certainty. This review evaluated whether p16^INK4A promoter methylation is associated with OSCC and OPMD.

Materials and methods: PubMed, Embase, Web of Science, Scopus, Livivo, and Google Scholar were searched. Studies were selected by title/abstract and then full-text review. Eligible studies investigated p16^INK4A methylation in OSCC or OPMD with comparator groups. Data were meta-analyzed using random-effects models to obtain pooled odds ratios (OR). Heterogeneity, publication bias, sensitivity analyses, and prediction intervals were assessed. Evidence certainty was rated using GRADE.

Results: Twenty-four studies were included, comprising 1330 OSCC patients, 606 OPMD patients, and 681 healthy controls. Meta-analyses demonstrated a strong association between p16^INK4A methylation and OSCC when compared with healthy controls (OR = 11.59; 95% CI = 6.01-22.37; p < 0.0001), with surgical margins (OR = 3.24; 95% CI = 1.86-5.65; p < 0.0001) and with OPMD (OR = 3.72; 95% CI = 2.47-5.59; p < 0.0001). OPMD also showed increased methylation versus healthy controls (OR = 24.8; 95% CI = 7.4-83.14; p < 0.0001).

Conclusions: p16^INK4A methylation is strongly associated with OSCC and OPMD; however, due to heterogeneity and low certainty of evidence, these findings should be interpreted cautiously. Further standardized, well-designed studies are needed to clarify the role of p16^INK4A methylation in oral carcinogenesis.

Trial registration: International Prospective Register of Systematic Reviews (PROSPERO): CRD42023410477.

Objective: To identify key clinical and therapeutic predictors of malignancy in a well-characterized, multicenter Spanish cohort of patients with Sjögren's disease (SjD).

Methods: A retrospective, cross-sectional study was conducted using data from the SjögrenSER-TRANS registry, a national cohort of 437 SjD patients from 33 Spanish hospitals who fulfilled the 2002 AECG classification criteria. Clinical, serological, and treatment-related variables were systematically collected. Descriptive statistics were used to summarize demographic and clinical characteristics. Bivariate analysis (chi-squared for categorical variables and t-tests for continuous variables) was performed to identify associations with malignancy (p < 0.05), followed by multivariate logistic regression to determine independent predictors.

Results: Malignancy was identified in 30 patients (6.86%), with gynecological cancers (30%) and lymphomas (23.3%) being the most common types. Independent predictors of malignancy included older age (OR 1.042, 95% CI 1.007-1.079), glandular inflammation (OR 2.888, 95% CI 1.281-6.512), and rituximab use (OR 3.959, 95% CI 1.461-10.730).

Conclusion: This study underscores the role of older age, glandular inflammation, and rituximab use as key risk factors for malignancy in SjD. However, the association with rituximab should be interpreted with caution, as indication bias cannot be ruled out. These findings emphasize the need for improved risk stratification and targeted surveillance strategies to facilitate early detection and enhance malignancy management in clinical practice. Prospective studies are warranted to refine monitoring protocols and optimize patient outcomes.

Introduction: While the prevalence of microsatellite instability (MSI) is low in the whole head and neck squamous cell carcinoma (HNSCC) population, it has been suggested to be more prominent in tumors of non-smokers. Therefore, the goal of this study was to determine the presence of MSI in a cohort of well-defined HNSCC of non-smokers and non-drinkers (NSND).

Methods: Clinical characteristics and tumor tissue of 119 NSND with HNSCC were retrospectively collected and analyzed for MLH1, PMS2, MSH2, and MSH6 protein expression on tissue microarrays (TMA). In case of negative staining for one of these mismatch repair proteins in the TMA cores, immunohistochemistry (IHC) was repeated on a whole slide section and additional molecular analyses were performed using polymerase chain reaction (PCR) and quantitative PCR (qPCR).

Results: Two cases showed dubious loss of MSH2 expression, one of these with concurrent dubious loss of MSH6 on the TMA. However, MSH2 and MSH6 expression was retained on whole slide sections and PCR and qPCR analyses did not show any mutations, compatible with a microsatellite stable result.

Conclusion: This study shows no single case with MSI in the NSND subgroup of HNSCC. Although a deficient DNA mismatch repair system is a predictive biomarker for response to immune checkpoint inhibitors, we found no evidence to support routine analysis of MSI in HNSCC, also not in the subgroup of NSND.

Objective: This study aimed to develop and evaluate Machine Learning models to predict the malignant transformation (MT) in patients with actinic cheilitis (AC).

Methods: Three hundred forty patients diagnosed with AC (322 in the no MT group, and 18 in the MT group) were carefully documented. The study used the Adaptive Synthetic Sampling to adaptively balance the dataset (322 in the no MT group and 319 in the MT group). Four supervised Machine Learning classifiers (Random Forest, Xtreme Gradient Boosting, Multilayer Perceptron, and Support Vector Machine) were trained and tested using 5-fold cross-validation to correlate inputs (clinical descriptors and demographic data) to outputs (MT). SHAP values were used to identify the most influential predictors of MT.

Results: The Xtreme Gradient Boosting model stood out, achieving 96.72% accuracy, 96.87% sensitivity, 96.57% specificity, 96.61% precision, 96.73% of F1-Score, and 0.9498 AUC. Multilayer Perceptron showed the best sensitivity (98.44%), and Random Forest presented comparable results. In contrast, Support Vector Machine underperformed, with higher values of false negatives and false positives. Across models, ulceration, multifocality, and long-standing lesions were the strongest predictors of MT, while small, asymptomatic, or solitary lesions were associated with lower risk.

Conclusion: The results revealed promising performance metrics for Xtreme Gradient Boosting and Multilayer Perceptron suggesting their potential value as tools in a support system for monitoring AC. Additionally, synthetic data proved constructive in training, enhancing the models' robustness and predictive capabilities.

Importance: Diprosopus is an exceedingly rare craniomaxillofacial dysmorphosis that is considered a subgroup of conjoined twins. This phenotype encompasses a broad spectrum of duplications ranging from partial structures to complete dicephalus. The embryogenesis and mechanism of disease are not well understood. The objective of this investigation was to describe a case of partial dentofacial duplication and to discuss the possible etiology with novel genetic insights thereof.

Observations: A newborn Kazakh boy was referred to the First Affiliated Hospital of Xinjiang Medical University because of a maxillary mass detected on prenatal imaging. Physical examination revealed a unilateral cleft lip and a soft lump around 2.5 cm in diameter with the appearance of an accessory upper lip. He underwent two surgical procedures at 11 months and 4 years of age for definitive treatment. He demonstrated favorable recovery outcomes, maintaining normal speech and oral intake capabilities during long-term follow-up.

Conclusions and relevance: Our preliminary findings and comprehensive literature review suggest that mutations in the PAX7 gene could contribute to the pathogenesis of craniofacial duplication. This hypothesis establishes a previously unrecognized association between specific genetic alterations and the clinical manifestations of this condition, potentially offering a molecular foundation for prenatal diagnostic approaches. The present case provides more profound insights into the disease mechanisms compared to prior reports. Further validation through basic scientific investigations and clinical studies, incorporating comprehensive genetic analyses, will be essential to substantiate this proposed mechanism.

Background: No studies to date have examined human papillomavirus (HPV) positivity in both odontogenic keratocysts (OKCs) and dentigerous cysts (DCs) or performed HPV genotyping in these lesions. This research aims to compare HPV expression rates in DCs and OKCs to provide insight into the molecular behavior of OKCs.

Methods: Forty DC and forty OKC cases were randomly selected and analyzed for HPV-DNA expression. Positive cases underwent HPV genotyping. Additionally an immunohistochemical staining for p16 was performed for each case.

Results: Due to epithelial integrity loss or inflammation, 18 samples were excluded, leaving 32 DCs and 30 OKCs for evaluation. HPV was detected in five DC cases but absent in all OKC samples. The difference between DC and OKC groups was not statistically significant (p = 0.053). Genotyping identified HPV-16 in four cases and HPV-66 in one.

Discussion: Despite OKCs' aggressive behavior, this study found no significant association between HPV and their pathogenesis. These findings suggest HPV is unlikely to contribute to OKC proliferation or recurrence, underscoring the need for larger studies to clarify its role in odontogenic cysts.

Background: The dynamic interplay between reactive free radicals (FR) and antioxidants (AO) can lead to either redox homeostasis or oxidative stress. Disruption of redox balance contributes to oxidative stress, a key factor in the pathogenesis of various conditions, notably oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). At low to moderate levels, FRs trigger adaptive mutations that initiate carcinogenesis and support neoplastic cell survival. In contrast, high concentrations of FRs exert cytotoxic effects, a mechanism exploited in radiotherapy and chemotherapy. Antioxidants counteract FRs, mitigating cellular damage-a benefit demonstrated in several clinical trials involving OPMDs. However, their efficacy in OSCC remains contentious.

Methods and finding: This review explores the multifaceted roles of FRs and AOs in OPMD and OSCC, with emphasis on their contributions to carcinogenesis and therapeutic strategies. Tracking the FR-AO ratio during treatment may offer predictive insights into malignant transformation and facilitate early OSCC detection.

Background: Mast cells are believed to contribute to inflammation-associated carcinogenesis, but their specific role in the development of oral leukoplakia (OLK) and its progression to oral squamous cell carcinoma (OSCC) remains uncertain. This systematic review and meta-analysis aimed to determine whether mast cell density differs among normal oral mucosa (NOM), OLK, and OSCC.

Methods: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science and Embase along with Google Scholar for studies that reported mast cell counts in OLK, OSCC, and NOM published up to September 30, 2025. Data were extracted, and the mean difference was calculated. Risk of bias was assessed using the JBI critical appraisal tool, and meta-analysis was performed using MetaAnalysisOnline.com.

Results: Thirty-four studies were included for qualitative and 26 contributed to quantitative data synthesis. The studies opined that mast cells were highest in OSCC, followed by OLK and NOM. Mast cell density was higher in OSCC than in OLK; however, the difference was not significant. A random-effects model revealed a significant increase in mast cell density in OLK than NOM (p < 0.0001) and OSCC than NOM (p = 0.0055); however, when OLK was compared with OSCC, the difference was not significant (p = 0.2865).

Conclusion: The existing data validate that mast cells were increased in oral leukoplakia, indicating their potential involvement in early oral carcinogenesis; however, future studies focusing on the prognostic value of mast cells in oral leukoplakia are warranted.

Trial registration: PROSPERO number: CRD42024533723.