Oral Epithelial Dysplasia Research Articles

Salivary Interleukin Levels in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia: Findings from a Sri Lankan Study.

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is paramount to improve patient outcome, and saliva testing is a promising non-invasive tool. The aim of this study was to assess salivary interleukins (lL1β, IL6, and IL8) in OSCC, OED and disease-free controls in a Sri Lankan study cohort. A case-control study with OSCC (n = 37), OED (n = 30) patients and disease-free controls (n = 30) was conducted. Salivary lL1β, IL6, and IL8 were quantified using enzyme-linked immuno-sorbent assay. Comparisons between different diagnostic groups and potential correlations to risk factors were assessed. Salivary levels for the three tested interleukins increased from disease-free controls through OED, and were highest in OSCC samples. Furthermore, the levels of IL1β, IL6, and IL8 increased progressively with OED grade. The discrimination between patients (OSCC and OED) and controls, as assessed by AUC of receiver operating characteristic curves, was 0.9 for IL8 (p = 0.0001) and 0.8 for IL6 (p = 0.0001), while IL1β differentiated OSCC from controls (AUC 0.7, p = 0.006). No significant associations were found between salivary interleukin levels and smoking, alcohol, and betel quid risk factors. Our findings suggest that salivary IL1β, IL6, and IL8 are associated with disease severity of OED, and are potential biomarkers for predicting disease progression in OED, and the screening of OSCC.

Lipid droplets’ functional protein caveolin-2 is associated with lipid metabolism-related molecule FABP5 and EMT marker E-cadherin in oral epithelial dysplasia

AimsTo explore the accumulation of lipid droplets (LDs) and its relationship with lipid metabolism, and epithelial-mesenchymal transition (EMT) in the carcinogenesis processes in the oral cavity.MethodsLDs were stained by oil...

Direct immunofluorescence cannot be used solely to differentiate among oral lichen planus, oral lichenoid lesion, and oral epithelial dysplasia

Background/purposeSome red and white lesions may have similar manifestations, making them difficult to be diagnosed. A direct immunofluorescence (DIF) assay can assist in making a final diagnosis of oral lichen planus (OLP). The aim of this study was to evaluate and compare the DIF profile in patients who had the clinical presentations of OLP and were histopathologically diagnosed with OLP, OLL (oral lichenoid lesion), or OED (oral epithelial dysplasia). Materials and methodsThe data were obtained from the medical records of 136 patients with the clinical presentations of OLP. Demographic information, histopathological diagnosis, malignant transformation, and DIF results were collected and analyzed. ResultsIn this study, 117 patients (86.0%) were DIF-positive, while 19 patients (14.0%) were DIF-negative. The highest DIF-positivity rate was in the OLP group (88.9%) followed by the OLL (83.7%), and the OED groups (81%). There were no significant differences in DIF-positivity rate, type of immunoreactants, location, or interpretation among these groups. Shaggy fibrinogen at the basement membrane zone (BMZ) was the most common DIF pattern in all groups. ConclusionThe DIF assay alone cannot be regarded as sufficient evidence for OLP, OLL, and OED differentiation. A histopathological examination is required to determine the presence of epithelial dysplasia or malignancy. To diagnose dysplastic lesions with the clinical manifestations of OLP, careful clinicopathologic correlation is mandatory. Due to the lack of scientific evidence to identify the primary pathology and the ongoing malignancy risk of epithelial dysplasia, meticulous long-term follow-up plays a crucial role in patient management.

SNAIL1 is involved in the control of the epithelial-mesenchymal transition in oral tongue squamous cell carcinoma

The aim of the present study was to investigate the role of SNAIL1, E-cadherin, and N-cadherin immunoexpression in oral tongue carcinogenesis. In addition, we evaluated in vitro the impact of silencing of the nuclear transcription factor SNAIL1 on the viability, apoptosis, proliferation, migration, and invasion of SCC-9 and HSC-3 cells. Immunohistochemical analysis of SNAIL1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia (OED) and 41 oral tongue squamous cell carcinoma (OTSCC). The suppression of SNAIL1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of SNAIL1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. Significant differences were observed in the expression of SNAIL1, E-cadherin, and N-Cadherin between OTSCC and OED. A low membrane expression of E-cadherin was strongly associated with poor overall survival in patients with OTSCC (P < .05), but the association did not withstand the Cox multivariate survival analysis. SNAIL1 silencing played a key role in the suppression of epithelial-mesenchymal transition and inhibited migration and invasion of HSC-3 cells (P < .0001, P < .01, respectively). In SCC-9 cells, SNAIL1 silencing promoted a significant reduction in the proliferation (P < .0001) and invasion (P < .0001). The epithelial-mesenchymal transition is present in different stages of oral tongue carcinogenesis, and SNAIL1 plays a key role in this process, although the underlying mechanisms still need to be elucidated. Thus, SNAIL1 might be a promising therapeutic target in OTSCC.

Quality of Life in Patients with Oral Potentially Malignant Disorders: Oral Lichen Planus and Oral Epithelial Dysplasia

Quality of Life in Patients with Oral Potentially Malignant Disorders: Oral Lichen Planus and Oral Epithelial Dysplasia

Expression and significance of m6A-RNA-methylation in oral cancer and precancerous lesion.

Oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) are a series of related pathologic and molecular events involving simple epithelial hyperplasia, mild to severe dysplasia and canceration. N6-methyladenosine RNA methylation, as the most common modification of both coding mRNA and non-coding ncRNA in eukaryotes, participates in the regulation of the occurrence and development of various malignant tumors in human. However, its role in oral epithelial dysplasia (OED) and OSCC remain unclear. In this study, multiple public databases were used for bioinformatics analysis of 23 common m6A methylation regulators in head and neck squamous cell carcinoma (HNSCC). Protein expressions of IGF2BP2 and IGF2BP3 were verified accordingly in clinical cohort samples of OED and OSCC. Patients with high expression of FTO、HNRNPC、HNRNPA2B1、LRPPRC、IGF2BP1、IGF2BP2、IGF2BP3 had a poor prognosis. IGF2BP2 had a relatively high mutation rate in HNSCC, and its expression was significantly positively correlated with tumor purity, and significantly negatively correlated with the infiltration level of B cells and CD8+T cells. The expression of IGF2BP3 was significantly positively correlated with tumor purity and CD4+T cells. Immunohistochemistrically, the expression of IGF2BP2 and IGF2BP3 in oral simple epithelial hyperplasia, OED and OSCC increased gradually. Both were strongly expressed in OSCC. IGF2BP2 and IGF2BP3 were the potential biological prognostic indicators of OED and OSCC.

Prognosis of oral epithelial dysplasia in individuals with and without oral lichen planus.

To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED). Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed. A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR=2.02, p= 0.04), which also developed faster (1.46 vs. 2.96 years, p= 0.04) and with more involvement of non-cancer-prone sites (p= 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.

Evolution tumour models paving the way for understanding oral carcinogenesis.

Throughout the centuries, the world's outstanding scientists and research groups have gathered their efforts to characterise the initiation and progression of malignant neoplasms. The temporal dissection of tumourigenesis provided by phylogenetic studies is one of the milestones in understanding cancer; however, some black boxes are still unsolved. Currently, there is no consensus regarding the development of oral squamous cell carcinoma (OSCC), the leading cancer of the head and neck region. Oral epithelial dysplasia (OED) may precede oral cancer and, occasionally, be clinically evident as white, red or mixed mucosal lesions, called oral potentially malignant disorders (OPMD). In a stepwise view of oral carcinogenesis, OED and OPMD have been considered harbingers of oral cancer. Nevertheless, the malignant transformation of OPMD is a rare event. Most of these disorders remain benign and can even regress, making it challenging to formulate evolutionary hypotheses for OSCC initiation. Deciphering OED evolution is vital to highlight the potential drivers of oral carcinogenesis and molecular targets for OSCC preventative and therapeutic strategies. This narrative review synthesises the main concepts of evolutionary theories and discusses which of them better explains OED development and malignant transformation.

GPR68 limits the severity of chemical-induced oral epithelial dysplasia

Head and neck cancer is the sixth most common malignancy, and there is an urgent need to identify physiological processes contributing to tumorigenesis. Extracellular acidification caused by aerobic glycolysis within tumor microenvironments can stimulate proton-sensing receptors. GPR68, or ovarian cancer G protein-coupled receptor 1, responds to extracellular acidity and is highly expressed in head and neck squamous cell carcinoma (HNSCC) as well as normal esophageal tissue. To study the role of GPR68 in oral dysplasia, wild-type and GPR68−/− mice were treated with 4-Nitroquinoline N-oxide (4NQO) in drinking water for 11–13 weeks, followed by normal water for 11–12 weeks. 4NQO treatment resulted in 45 percent of GPR68−/− mice developing severe dysplasia or squamous cell carcinoma compared to only 10.5 percent of GPR68+/+ mice. This correlated with increased frequencies of regulatory T cells in the spleens of male GPR68−/− mice. Dysplastic regions of the tongue had increased CD31 staining compared to normal regions in both GPR68−/− and GPR68+/+ mice, suggesting that angiogenesis was GPR68-independent. RNA knockdown studies using HNSCC cell lines demonstrated no direct effect of GPR68 on survival or growth. Overall, we demonstrate that GPR68-deficiency worsens the severity of chemical-induced oral dysplasia, suggesting a protective role for this gene in tumorigenesis.

FGFR1 is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridizationin the tongue squamous cell carcinoma cases. Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p=0.016, HR: 7.3, 95% CI: 1.4-37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease-free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p=0.024; HR: 4.9, 95% CI: 1.2-19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n=8) showed markedly impaired overall survival (p=0.020; HR: 6.4, 95% CI: 1.3-31.1) and disease-free survival (p=0.001, HR: 13.0, 95% CI: 3.0-55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p=0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease-free survival. Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.

MUC4 Expression in Oral Dysplastic Epithelium and Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

MUCIN4 (MUC4) glycosylation is linked to the oncogenesis and progression of a neoplastic process. It can suggest information pertaining to tumor progression, management and its natural properties. Thus, MUC4 can play a pivotal role in prognostic diagnosis. This study aimed to analyze the MUC4 expression in oral cell squamous carcinoma and oral dysplastic epithelium. The research included 45 samples of oral epithelial dysplasia (OED) and 45 cases of oral squamous cell carcinoma (OSCC). In order to carry out the investigation, tissue blocks of previously diagnosed cases of OED and OSCC were retrieved from the relevant archives. Forty-five OED cases were categorized into three group's mild, moderate and severe dysplasia, with 15 cases in each respective category. Forty-five OSCC cases were categorized into three groups: well differentiated, moderately differentiated, and poorly differentiated OSCC with 15 cases in each respective category. Ten tissue biopsies of normal oral mucosa were obtained from subjects in the control group. The chi-square test and one-way ANOVA were used for statistical analysis. There was an absence of MUC4 expression in normal mucosa, whereas the OED and OSCC groups had a significant amount of observable variance. Within the OED category of cases, a consistent progression from mild to severe dysplasia was seen in terms of the staining pattern. Cases with severe dysplasia displayed a staining pattern that covered the complete thickness of the tissue in the epithelium. Expression of MUC4 was shown to be lower in moderate differentiated squamous cell carcinoma (MDSCC), and poorly differentiated squamous cell carcinoma (PDSCC) as compared to well differentiated squamous cell carcinoma (WDSCC). It showed decreasing pattern across all grades of OSCC. In WDSCC, an intense highest staining response was noticed, particularly among the cells that are highly differentiated and take the form of a honeycomb pattern. Analysis of the expression profile of MUC4 and the aberrant expression of this gene in OSCC suggests that it may serve as a useful diagnostic marker. Therefore, it is possible to draw the conclusion that MUC4 plays a very significant part in the pathogenesis of OSCC and also acts as a marker that may be taken into consideration for the accurate diagnosis of OED and OSCC.

Elastin remodeling: Does it play a role in priming the malignant phenotype of oral mucosa?

The extracellular matrix (ECM) is a dynamic tissue that provides nutrition and support to overlying epithelium. During tumorigenesis, the tumor microenvironment (TME) dysregulates the ECM. This is reflected by morphological changes seen in collagen and elastic fibers and is thought to facilitate metastasis. To study the degradation of elastic fibers in different grades of oral squamous cell carcinoma (OSCC) and in oral epithelial dysplasia (OED) using histochemistry and to correlate it to the TNM stage of OSCC. Tumor cores from 38 cases of OSCC (well-differentiated[15], moderately differentiated[14], and poorly differentiated[9]) and 15 incisional biopsies of OED were analyzed. Hematoxylin-eosin and Verhoeff's-Van Gieson (VVG) stains were used. The stained sections were assessed for morphological changes in elastic fibers. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 22 software. Fisher's exact, Kruskal-Wallis, one-way ANOVA, and Turkey post hoc tests were used to establish significance (P ≤ 0.05). Spearman's correlation test was used to correlate elastin fiber degradation with TNM stage of OSCC. All grades of OSCC showed absence of elastic fibers around the tumor islands. Elastic fiber degradation (fragmented and clumped type fibers) increased proportionately with the grade and TNM stage of OSCC. In OED, A significant reduction in the amount of elastic fibers with increasing grade was noted. A positive correlation was noted between elastin degradation and grade and stage of OSCC. Therefore, it may be implicated in tumor progression of OSCC.

Deep learning approach to detect high-risk oral epithelial dysplasia: A step towards computer-assisted dysplasia grading

Introduction: Oral epithelial dysplasia (OED) is associated with high interobserver and intraobserver disagreement. With the exponential increase in the applicability of artificial intelligence tools such as deep learning (DL) in pathology, it would now be possible to achieve high accuracy and objectivity in grading of OED. In this research work, we have proposed a DL approach to epithelial dysplasia grading by creating a convolutional neural network (CNN) model from scratch. Materials and Methods: The dataset includes 445 high-resolution ×40 photomicrographs captured from histopathologically diagnosed cases of high-risk dysplasia (HR) and normal buccal mucosa (NBM) that were used to train, validate and test the two-dimensional CNN (2DCNN) model. Results: The whole dataset was divided into 60% training set, 20% validation set and 20% test set. The model achieved training accuracy of 97.21%, validation accuracy of 90% and test accuracy of 91.30%. Conclusion: The DL model was able to distinguish between normal epithelium and HR epithelial dysplasia with high grades of accuracy. These results are encouraging for researchers to formulate DL models to grade and classify OED using various grading systems.

Genome sequencing reveals molecular subgroups in oral epithelial dysplasia.

This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

Whole-exome sequencing of oral epithelial dysplasia samples reveals an association with new genes.

The genetic basis of oral epithelial (OED) is unknown, and there is no reliable method for evaluating the risk of malignant transformation. Somatic mutations are responsible for the transformation of dysplastic mucosa to invasive cancer. In addition, these genomic variations could represent objective markers of the potential for malignant transformation. We performed whole-exome sequencing of 10 OED samples from Brazilian and Chilean patients. Using public genetic repositories, we identified 41 deleterious variants that could produce high-impact changes in the amino acid structures of 38 genes. In addition, the variants were filtered according to normal skin and Native American genome profiles. Finally, 13 genes harboring 15 variants were found to be exclusively related to OED. High-grade epithelial dysplasia samples showed a tendency to accumulate highly deleterious variants. We observed that 62% of 13 OED genes identified in our study were also found in head and neck squamous cell carcinoma. Among the shared genes, eight were not identified in oral squamous cell carcinoma. To our knowledge, we have described for the first time 13 genes that are found in OED in a Latin American population, of which five genes have already been observed in oral squamous cell carcinoma. Through this study, we identified genes that may be related to basal biological functions in OED.

Effect of ethanol extract from Chrysanthemum cinerariifolium leaves on Ki-67 proliferation and dysplasia severity in a rat model of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that can rapidly infiltrate the oral epithelial tissue and cause high mortality worldwide because the available therapies are less effective. Chrysanthemum cinerariifolium leaf contains secondary metabolites as anti-inflammatory, antioxidant, anticancer, and antimutagenic. The study aimed to analyze the ethanolic extract of C. cinerariifolium leaf in reducing proliferation (Ki-67) and the degree of dysplasia in OSCC rats. This study used male Sprague Dawley induced by 7,12-dimethylbenz(a)anthracene (DMBA) 0.5% and divided into five treatment groups, namely positive control/C+ (sick), negative control/C- (healthy), and treatment group induced with DMBA and given extract C. cinerariifolium leaf with successive doses of T1, T2, and T3 (50, 100, and 200 mg/kg bw). The oral epithelium was stained with hematoxylin and eosin and immunohistochemically stained with a Ki-67 monoclonal antibody. The statistical analysis utilizes the one-way analysis of variance test. The results showed that T1 at a dose of 200 mg/kg bw could significantly reduce Ki-67 expression and the degree of oral epithelial dysplasia (OED; p < 0.05) close to healthy controls. The conclusion shows that C. cinerariifolium leaf extract can be a therapy against OSCC by decreasing cell proliferation and the degree of OED.

Salivary miRNAs Expression in Potentially Malignant Disorders of the Oral Mucosa and Oral Squamous Cell Carcinoma: A Pilot Study on miR-21, miR-27b, and miR-181b

(1) Background: Oral potentially malignant disorders (OPMD) represent a fundamental challenge for clinicians, considering the possibility of progression into oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Several studies have examined the expression of miRNAs in humans as diagnostic and prognostic biomarkers. Among these, miR-21, miR-27b, and miR-181b proved to be promising. This cohort study evaluated the different expressions of those miRNAs in the saliva of patients with OPMD and OSCC. (2) Methods: Patients with a clinical diagnosis of OPMD and/or OSCC were enrolled; saliva samples were collected; miRNAs were extracted and quantified via qRT-PCR was performed. Data were analyzed by subgroups based on the histopathological diagnosis (OSCC and the grade of OED) using the ΔΔCt method. Saliva from 10 healthy donors was used as the control. One-way ANOVA and Kruskal-Wallis tests were performed to assess the differences between groups. (3) Results: 23 patients for the OPMD group (6 with no dysplasia, 7 with low-grade, and 10 with high-grade dysplasia) and 10 with OSCC were analyzed. MiR-21 did not show any variation among groups; miR-27b was under-expressed in dysplastic lesions (p = 0.046); miR-181b was upregulated in high-grade dysplasia (p = 0.006), increasing with the degree of dysplasia, and decreasing in OSCCs. (4) Conclusions: Salivary miR-27b and miR-181b could be promising biomarkers for oral dysplasia. Further studies are needed to clarify their feasibility.

Expression of Minichromosome Maintenance Protein 2 (MCM2) in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma: A Systematic Review.

The online version contains supplementary material available at 10.1007/s12070-022-03296-7.

Heat Shock Protein 27 (HSP27) as a Potential Prognostic Marker: Immunohistochemical Analysis of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

To evaluate and correlate the expression of heat shock protein 27 (HSP27) in oral epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC). This immunohistochemical study of HSP27 expression was performed on 45 samples retrieved from the departmental archives. It included 15 cases of oral ED, 15 cases of OSCC and 15 cases of epithelial hyperplasia (EH). The staining intensity and distribution were scored. The expression was compared between the study groups. Kruskal-Wallis Test, Mann-Whitney U Test and Chi-square tests were performed for statistical analysis using SPSS v21.0 (IBM Corp., Armonk, NY, USA). Results: There was a statistically significant difference in HSP27 staining parameters between EH, oral ED and OSCC. There was no significant difference between oral ED and OSCC. Conclusion: HSP27 expression shows enhanced expression in oral ED and OSCC. Its expression should be investigated using larger sample sizes with clinico-pathological correlation to prove its efficiency as a prognostic marker. It will help us in defining treatment modalities so that mortality and morbidity associated with OSCC could be reduced.

Assessment of the Relationship between Expressions of CD34, p63 with Different Clinical Types of Oral Epithelial Dysplasia: A Retrospective Immunohistochemical Study

Background: Potentially malignant disorders such as leukoplakia and erythroplakia are often associated with dysplastic changes that have an increased risk for malignant transformation. CD34 is considered as an important marker for tissue vascularization, which represents microvessel density. P63 has a role in epithelial proliferation and is frequently altered in dysplasia and associated with tumorigenesis. The aim of this study was to evaluate the expression of CD34 and p63 in different grades of oral epithelial dysplasia (OED). Methods and Results: This research included 50 histopathologically confirmed OED. CD34 and P63 expressions were studied by using the immunohistochemical technique. Most OED lesions were observed in patient between 40 and 69 years of age. Buccal mucosa was the most affected site (42%). According to histopathological grades, mild OED was predominant (54%). There was a significant difference among OED grades through the P63 marker. Conclusion: The P63 marker can be considered a good indicator for malignant transformation by grade scoring scales, and the CD34 marker can be used as a useful diagnostic indicator for OED.