Expression of invadopodia markers can identify oral lesions with a high risk of malignant transformation

What are the surveillance recommendations following resection of sinonasal inverted papilloma?

Aldehyde dehydrogenase 1 expression correlated with malignant potential of oral lichen planus

Oral epithelial dysplasia is histopathologically characterised by morphological and cellular changes. It is the most important predictive risk factor for progression into invasive neoplasm. Architectural and cytopathological characteristics have been updated by the World Health Organization in 2022. In India, The prevalence rate of OED and OSCC was 5.71% and 9.85% respectively. The aim of the study is to analyse and correlate the clinicopathological risk factors associated with malignant transformation in patients diagnosed with oral epithelial dysplasia (OED). We have attempted to classify the OED based on age, sex, site and associated habits and malignant transformation rate. In this study, clinical data of 165 cases diagnosed histopathologically as oral epithelial dysplasia (OED) were retrieved from the Dental Information Archival Software (DIAS), Saveetha Dental College and Hospital, a total of 1367 cases reported between 2015 and 2018. The patient's age, gender, anatomical site of biopsy, habit history and histopathological diagnosis were tabulated. Out of the 165 diagnosed OED cases, 46 cases that met the inclusion criteria and had complete follow-up data for 36 months were included in the final analysis. Cases with incomplete clinical records, loss to follow-up, or concurrent malignancies at initial diagnosis were excluded. Data were analysed using SPSS software v23 (IBM, Armonk, NY, USA) with ANOVA and Independent t-test. A cohort of 46 cases with OED were followed up for 36 months. At the time of initial diagnosis, 36% (n = 17) of the cases had severe epithelial dysplasia, 34% (n = 16) of cases had moderate epithelial dysplasia, and 28% (n = 13) of cases had mild epithelial dysplasia. After 36 months of follow-up, 8 cases exhibited clinical features suggestive of malignant transformation-such as non-healing ulceration, induration, increased lesion size, erythematous changes, and altered surface texture. Based on these findings, they were advised to undergo a second biopsy for histopathological confirmation. Of the 8 cases that underwent a second biopsy, 3 cases (8%) showed histopathological evidence of malignant transformation to oral squamous cell carcinoma (OSCC), characterized by invasive epithelial islands breaching the basement membrane, cellular atypia, and keratin pearl formation. These included previously diagnosed Moderate OED (n = 1) and Severe OED (n = 2). In contrast, the remaining 5 cases (10%) continued to exhibit dysplastic changes without evidence of invasion-comprising Moderate OED (n = 1) and Severe OED (n = 4)-and were therefore not considered malignant transformations. The remaining (82%) did not show any clinical change. There was no evidence of regression of lesions in the second biopsy. To conclude, we observed the highest risk of malignant transformation in OED to OSCC within the first three years after initial diagnosis. Male patients, patients with a combination of deleterious habits, and patients with histologically severe grades of OED had an increased risk of malignant transformation. Further multicentric studies with larger cancer registries and studies on prognostic immunohistochemical markers can help us in deciphering the pathogenesis of OED into OSCC.

Premalignant lesions of the oral cavity: a narrative review of factors and mechanisms of transformation into cancer.

MicroRNA-based classifiers for diagnosis of oral cavity squamous cell carcinoma in tissue and plasma

MAGE-A expression in oral and laryngeal leukoplakia predicts malignant transformation

Alterations of the P53 gene and human papillomavirus (HPV) infection are associated with development of oral squamous cell carcinoma (OSCC). We aimed to identify mutation of P53 exon 8 codon 282 in OSCC and correlate these with HPV infection as well as histopathological grade of OSCC. Samples of known HPV infection status were studied including oral lesion cells, formalin-fixed paraffin embedded (FFPE) tissues from OSCC and exfoliated oral cells of matched age-sex controls. P53 exon 8 mutation was detected using the polymerase chain reaction (PCR). Mutation of codon 282 was identified by allele-specific oligonucleotide typing (ASO) using EvaGreen real-time PCR. The PCR products were analyzed by gel electrophoresis and melting curve analysis. Mutation of P53 exon 8 was seen in 81.7% and 69.6% of FFPE OSCC tissues and oral lesion cells, respectively. This was significantly higher than in controls (16.7%). Frequency of mutation did not differ between HPV-positive samples (62.5% and 81.8% in oral lesion cells and FFPE tissue samples, respectively) and HPV-negative samples (73.3% and 81.5% in oral lesion cells and FFPE tissue samples, respectively). This finding is similar to P53 codon 282 mutation that was found only in FFPE tissues (35.0%) and oral lesion cells (32.6%) from both HPV-positive and negative OSCC. Interestingly, frequency of mutation was higher in well-differentiated OSCC with HPV-infection (28.1%) than without HPV (14.8%). This result demonstrated a mutation hot spot in P53 associated with oral carcinogenesis and might be useful to guide chemotherapeutic modality for HPV-associated OSCC in northeast Thailand.

Oral potentially malignant disorders (OPMD) include a variety of mucosal lesions such as oral lichen planus (OLP), oral lichenoid lesions (OLL) and oral lichenoid dysplasia (OLD). Their rate of malignant transformation ranges from 0% to 34% and is dependent on OPMD type, lesion site and a range of risk factors. This study seeks to determine the proportion of oral lichenoid conditions that transform into oral squamous cell carcinoma (OSCC) in an Australian population. The study is a retrospective audit of patients from a private oral medicine clinic, diagnosed with OLP, OLL or OLD using clinical and histopathological data between 2006 and 2014. Patients were cross-matched with Cancer Registry data for OSCC, and the rate and time to malignant transformation determined. OLP and OLL patients displayed a low risk of malignant transformation; 0.49% (1/206) for OLP and 0% (0/31) for OLL. In contrast, OLD patients, all of whom presented clinically as OLP, were at much higher risk with 6.81% (3/44) developing OSCC over an average time of 4.6years (±2.4 SD). Rates of smoking and alcohol consumption were no higher in OLD patients compared to others. Compared with other oral lichenoid conditions, OLD lesions are at a particularly high risk of malignant transformation and should be managed based on the presence of dysplasia and not the lichenoid inflammatory infiltrate. OLP demonstrates a relativelylow rate of malignant transformation. Diagnostic histopathology is important for discriminating OLP from OLD.

Oral squamous cell carcinoma (OSCC) is a malignancy that affects the oral mucosa and is characterized by indurated oral lesions. The RNAseq of formalin-fixed, paraffin-embedded (FFPE) samples is readily available in clinical settings. Such samples have long-term preservation and can provide highly accurate transcriptomic information regarding gene fusions, isoforms, and allele-specific expression. We determined differentially expressed genes using the transcriptomic profiles of oral potentially malignant disorder (OPMD) FFPE oral lesion samples of patients who developed OSCC over years. A technical comparison was completed comparing breast cancer (BC) FFPE publicly available data in this proof-of-concept pilot study. OSCC FFPE samples were collected from patients (N = 3) who developed OSCC 3 to 5 years following OPMD diagnosis (n = 3) and were analyzed using RNAseq. RNAseq sequences from the FFPE OSCC samples and publicly available FFPE samples of BC patients (n = 6) (Gene Expression Omnibus Database, GSE58135) aligned to human reference (GRCh38.p13). Genes were counted using the Spliced Transcripts Alignment to a Reference (STARv2.7.9a) software. Differential expression was determined in R using DESeq2v1.40.2 comparing OSCC to BC samples. Principal component analysis (PCA) plots were completed. Differential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined via the Pathviewv.1.40.0 program. STRING v12.0 was used to determine protein-protein interactions between genes represented in more than one KEGG pathway. STARv2.7.9a identified 27,237 and 30,343 genes among the OSCC and BC groups, respectively. DESeq2v1.40.2 determined 9194 differentially expressed genes (DEPs), 4466 being upregulated (OSCC > BC) and 4728 being downregulated (BC > OSCC) (padj < 0.05). Most significant genes included KRT6B, SERPINB5, and DSC3 (5- to 10-fold change range; padj < 10 × 10-100). PCA showed that BC and OSCC samples clustered as separate groups. Pathviewv.1.40.0 identified 17 downregulated KEGG pathways in OSCC compared to the BC group. No upregulated KEGG pathways were identified. STRINGv12.0 determined Gene Ontology Biological Process enrichments for leukocytes and apoptosis in upregulated KEGG genes including multiple PIK3 genes and NIK/NF-kappaB signaling and metabolic responses from lipopolysaccharides in downregulated KEGG genes including CHUK and NFKB1. Using FFPE samples, we determined DEPs characteristic of OSCC and distinct from BC. KRT-family genes and lipopolysaccharide producing periodontal pathogens may be further investigated for their involvement in the OPMD to OSCC transition.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer with a poor prognosis. Oral epithelial dysplasia (OED) is a precancerous lesion associated with an increased risk of malignant transformation (MT) into OSCC. However, current histopathological methods for diagnosing OED are subjective and ineffective in assessing MT risk. FTIR provides a comprehensive biochemical profile of tissues, known as "biomolecular fingerprinting". Previously we developed an FTIR-based OSCC-Benign classifier that accurately distinguishes OSCC from benign tissue. In this study, we evaluated whether this classifier could also predict MT risk in OED. Thirty OED patient biopsies with documented MT outcomes were analyzed, including 12 with and 18 without MT. FTIR images were acquired from six regions of interest (ROIs) per tissue section, yielding an average epithelial spectrum for each ROI, and a total of 180 spectra for model evaluation. The OSCC-Benign classifier achieved an accuracy of 81.7% with an F1 score of 0.77 at the ROI level, and an accuracy of 83.3% with an F1 score of 0.8 at the biopsy level in predicting MT in OED. Our findings suggest that OEDs with biomolecular fingerprints similar to OSCC carry a higher risk of MT, while those resembling benign tissue carry a lower risk, providing new insight into the malignant transformation process. In summary, the FTIR-based machine learning approach outperforms traditional histopathology in predicting MT risk in OED, potentially offering a quantitative and objective tool for clinical diagnosis.

Oral submucous fibrosis (OSMF) is considered to be a potentially malignant oral disorder with high risk of malignant transformation. Oral squamous cell carcinoma (OSCC) arising from OSMF has peculiar clinical and histopathological features. To assess the clinicopathological features of OSCC arising in the background of OSMF in an attempt to identify the patients with OSMF who are at increased risk of developing OSCC. A systematic review was performed based on PRISMA guidelines to include articles published until May 2021 in English, relating the clinicohistopathological characteristics of OSCC arising from OSMF (OSMF-OSCC) or OSMF associated with OSCC (OSCC-OSMF). All the eligible articles were analyzed and relevant data were extracted. Seventeen articles were included for systematic review after following strict inclusion and exclusion criteria. The malignant transformation rate of OSMF-OSCC ranged from 1.9 to 9.13 and the prevalence of OSCC-OSMF ranged from 2.8 to 66. The mean age of the patients ranged from 36.6 years to 47.2 years and buccal mucosa was the common site to be affected. Majority of the OSCC-OSMF was well-to-moderately differentiated and majority of them did not metastasize to the lymph nodes. OSCC associated with OSMF presents at a younger age with early tumor stage, better differentiation, and better prognosis when compared to OSCC not associated with OSMF. However, more multicentric prospective studies with large sample size are required to determine the true biologic behavior of OSCC arising in the background of OSMF to establish less aggressive treatment strategies considering them as a separate entity.

This work demonstrates that a comprehensive strategy of proteomics identification combined with further validation and detailed functional analysis should be adopted in the field of cancer biomarker discovery. A comparative proteomics approach was utilized to identify differentially expressed proteins in 10 oral squamous carcinoma samples paired with their corresponding normal tissues. A total of 52 significantly and consistently altered proteins were identified with eight of these being reported for the first time in oral squamous carcinoma. Of the eight newly implicated proteins, RACK1 was chosen for detailed analysis. RACK1 was demonstrated to be up-regulated in cancer at both the mRNA and protein levels. Immunohistochemical examination showed that the enhanced expression of RACK1 was correlated with the severity of the epithelial dysplasia as well as clinical stage, lymph node involvement, and recurrence, which are known indicators of a relatively poor prognosis in oral squamous carcinoma patients. RNA interference specifically targeted to silence RACK1 could initiate apoptosis of oral squamous carcinoma cells. Taken together, the results indicate that RACK1 is up-regulated in oral squamous carcinoma, not only being closely related to cell proliferation and apoptosis but also linked to clinical invasiveness and metastasis in carcinogenesis. The observations suggest that RACK1 may be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of oral squamous carcinoma. Further this comprehensive strategy could be used for identifying other differentially expressed proteins that have potential to be candidate biomarkers of oral squamous carcinoma.

Basal Ki67 expression measured by digital image analysis is optimal for prognostication in oral squamous cell carcinoma

Background: Oral Potentially Malignant Disorders (OPMDs) pose a significant risk for progression into Oral Squamous Cell Carcinoma (OSCC), a leading cause of oral cancer-related mortality. Early detection and risk assessment are critical for timely intervention. This meta-analysis evaluates predictive biomarkers, clinical features, and chemoprevention strategies influencing the malignant transformation of OPMDs to OSCC. Methods: A systematic literature search was conducted across PubMed, Web of Science, Cochrane Library, and Scopus databases following PRISMA guidelines. Studies evaluating biomarkers, histopathological features, or chemopreventive treatments for OPMDs were included. Randomized controlled trials (RCTs), phase I and II clinical trials, and observational studies were analyzed. Statistical analysis, including heterogeneity assessment and bias evaluation, was performed using R software. Results: A total of 10 studies with 980 participants were included. PD-L1 expression, EGFR mutations, and histopathological dysplasia were identified as key predictive biomarkers, with PD-L1 showing a sensitivity of 80% and specificity of 75% for malignant transformation. Targeted therapies such as Nivolumab, Erlotinib, and chemopreventive agents, including Green Tea Extract and Vitamin A, demonstrated significant reductions in lesion progression. Smoking, betel quid use, and genetic mutations were strongly correlated with increased OSCC risk. Conclusions: This meta-analysis confirms that integrating predictive biomarkers with clinical risk assessment can enhance early detection and intervention for OPMDs at high risk of malignant transformation. Chemoprevention strategies show variable effectiveness, highlighting the need for individualized therapeutic approaches. Future research should focus on refining biomarker-based screening protocols and optimizing targeted chemoprevention to mitigate OSCC progression risk.

MicroRNA-375 as a biomarker for malignant transformation in oral lesions