Oral Epithelial Dysplasia Lesions Research Articles

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.

Prediction of malignant transformation in oral epithelial dysplasia using infrared absorbance spectra.

Oral epithelial dysplasia (OED) is a histopathologically-defined, potentially premalignant condition of the oral cavity. The rate of transformation to frank carcinoma is relatively low (12% within 2 years) and prediction based on histopathological grade is unreliable, leading to both over- and under-treatment. Alternative approaches include infrared (IR) spectroscopy, which is able to classify cancerous and non-cancerous tissue in a number of cancers, including oral. The aim of this study was to explore the capability of FTIR (Fourier-transform IR) microscopy and machine learning as a means of predicting malignant transformation of OED. Supervised, retrospective analysis of longitudinally-collected OED biopsy samples from 17 patients with high risk OED lesions: 10 lesions transformed and 7 did not over a follow-up period of more than 3 years. FTIR spectra were collected from routine, unstained histopathological sections and machine learning used to predict malignant transformation, irrespective of OED classification. PCA-LDA (principal component analysis followed by linear discriminant analysis) provided evidence that the subsequent transforming status of these 17 lesions could be predicted from FTIR data with a sensitivity of 79 ± 5% and a specificity of 76 ± 5%. Six key wavenumbers were identified as most important in this classification. Although this pilot study used a small cohort, the strict inclusion criteria and classification based on known outcome, rather than OED grade, make this a novel study in the field of FTIR in oral cancer and support the clinical potential of this technology in the surveillance of OED.

Loss of FANCD2 and related proteins may predict malignant transformation in oral epithelial dysplasia

Predicting malignant transformation (MT) in oral epithelial dysplasia (OED) is challenging. The higher rate of MT reported in nonsmokers suggests an endogenous etiology in oncogenesis. We hypothesize that loss of FANCD2 and associated proteins could influence genomic instability and MT in the absence of environmental carcinogens. Longitudinal archival samples were obtained from 40 individuals with OED: from diagnosis to the most recent review in 23 patients with stable OED or until excision of the squamous cell carcinoma in 17 patients with unstable OED undergoing MT. Histopathological reassessment, immunohistochemistry for FANCD2, and Western blotting for phosphorylation/monoubiquitylation status of ATR, CHK1, FANCD2, and FANCG were undertaken on each tissue sample. Decreased expression of FANCD2 was observed in the diagnostic biopsies of OED lesions that later underwent MT. Combining the FANCD2 expression scores with histologic grading more accurately predicted MT (P=.005) than histology alone, and it correctly predicted MT in 10 of 17 initial biopsies. Significantly reduced expression of total FANCD2, pFANCD2, pATR, pCHK-1, and pFANCG was observed in unstable OED. There is preliminary evidence that defects in the DNA damage sensing/signaling/repair cascade are associated with MT in OED. Loss of expression of FANCD2 protein in association with a higher histologic grade of dysplasia offered better prediction of MT than clinicopathologic parameters alone.

Immunosurveillance profile of oral squamous cell carcinoma and oral epithelial dysplasia through dendritic and T-cell analysis.

To evaluate the profile of dendritic (Langerhans and plasmacytoid) and T cells in OSCC and oral epithelial dysplasia (OED) and correlate these findings with clinical data. Fifty cases of OSCC and 48 of OED were immunostained for CD1a and CD83 dendritic Langerhans cells (DLC), CD303 plasmacytoid dendritic cells (pDC) and CD8 followed by quantitative analysis. Analysis revealed a significant decrease in the number of mature CD83 DLC in OSCC compared with OED. CD303 positivity was significantly increased in the OSCC group when compared to OED. CD8-positive lymphocytes were significantly decreased in OSCC compared with OED lesions. No statistical correlation was found with clinical data. The number of mature dendritic cells (DC) was decreased in OSCC compared with OED lesions suggesting that either these cells might have migrated to lymph nodes to present the tumour antigens and activate the immune system or cytokines secreted by the tumour microenvironment are inhibiting the adequate maturation of DLC. The numbers of pDC were significantly increased in the OSCC group compared with the OED group. This suggests they may play an important role in the defence against tumours although it is not clear whether this is promoting or inhibiting malignant progression.

Langerhans cell counts in oral epithelial dysplasia and their correlation to clinicopathological parameters.

Langerhans cells (LCs) are antigen presenting cells. This study assessed the LC counts in oral epithelial dysplasia (OED) and their correlation to clinicopathological parameters. This study examined the LC counts in the epithelia and subepithelial connective tissues of 58 patients with OED (21 mild, 18 moderate, and 19 severe OED lesions) and 10 specimens of normal oral mucosa (NOM) by anti-S-100 protein immunostaining. We found that the mean LC counts in the epithelia or subepithelial connective tissues increased significantly from NOM samples through mild and moderate OED to severe OED samples. In addition, a significant correlation was found between higher mean LC counts in the dysplastic epithelia of OED samples and OED lesions with thicker epithelial layers (p<0.001) or wider inflammatory zones (p<0.001), and between higher mean LC counts in the subepithelial connective tissues of OED samples and OED lesions with wider inflammatory zones (p<0.001). Moreover, the nine OED lesions with malignant transformation had a significantly lower mean LC count than the 49 OED lesions without malignant transformation. The significant and gradual elevation in LC count from NOM through mild and moderate OED to severe OED lesions suggests an upregulation of immunosurveillance ability in OED patients during the early oral carcinogenesis process. A low LC count in OED lesions may suggest the partial loss of immunosurveillance ability against dysplastic cells; this in turn favors the malignant transformation of an OED lesion into oral cancer.

Evaluation of Microvascular Density as a Predictive Indicator for Malignant Transformation of Oral Epithelial Dysplasia (OED)

While not all OED lesions will transform, approximately one third of OED lesions progress to oral squamous cell carcinoma (OSCC). Provided the poor overall prognosis for OSCC patients, intervention at the premalignant stage of OED is an attractive clinical strategy. We do not, however, currently have biomarkers to identify the most aggressive premalignant lesions. Identification of suchbiological indicators would allow for targeting of OED lesions with high transformation risk and direct lesional-specific management e.g.

Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: An attempt to understand the sources of variation

The present study attempted to assess the reasons behind the inter-observer variation in grading oral epithelial dysplasia (OED). Three oral pathologists and one general pathologist examined 68 histological slides of OED lesions of variable grade for scoring the presence of each individual characteristic of the architecture and cytology changes that were established by the 2005 WHO classification. The assigned features in each case were correlated with clinical outcomes to understand which features are more commonly associated with malignant transformation. Interestingly, for all individual characteristics, the pairwise inter-examiner and group kappa values ranged from poor to moderate. It appeared that for each characteristic separately there was much dissension. Despite these observations, comparing these data with that from our previous paper on the same slides showed that the inter-observer agreement on the degree of dysplasia either by using the new binary system of "low-risk" or "high-risk" or by using the 2005 WHO classification turned out to be better than the agreement on the individual characteristics of architecture and cytology changes. Certain features show significant association with the clinical outcomes. In the discussion, some explanations to help understanding the sources of variation in grading OED are put forward. In conclusion, grading dysplasia is not an exact science and pathologists are doing their best to reach optimal results. Improvement in the standard of the histopathology reporting of OED lesions could be achieved by consideration of several issues. Of these, there is need for a universal definition of the architectural and cytological features that are the basis of any OED grading process. A minimum dataset for reporting OED lesions should be set up. Also, the use of a consensus scoring process between two or more observers should be encouraged as this would improve inter-observer agreement.