Malignant Potentiality Of Oral Submucous Fibrosis Research Articles

Evaluation of Salivary Superoxide Dismutase Levels in Oral Submucous Fibrosis – A Cross Sectional Study

Background: Oral Submucous Fibrosis (OSMF) is a potentially malignant disorder with areca nut being the main etiological agent. Increased risk of malignant potential of OSMF necessitates the early diagnosis of the condition. Superoxide dismutase (SOD) scavenges oxygenated free radicals and can be used as a potential biomarker for oral cancer detection.
 Objectives: The present study was conducted to estimate and compare salivary SOD levels in patients with OSMF and healthy controls and to compare its levels in different clinical and functional stages of OSMF.
 Methodology: The study group (Group 1) included 30 patients of OSMF, and the control group (Group 2) was formed by age and sex-matched healthy individuals. Salivary SOD levels were determined by Nitro Blue Tetrazolium (NBT) chloride method. The levels of salivary SOD were compared between the two groups and the data thus obtained was subjected to statistical analysis using independent sample t-test and one way Analysis of variance (ANOVA) test.
 Results: The mean salivary SOD in the study group was 0.583 IU/mL and 0.864 IU/mL in control group and the difference was found to be statistically significant. Thus, the patients with OSMF had significantly lower levels of salivary SOD compared to the controls.
 Conclusion: The decrease in the salivary SOD levels in patients with OSMF suggests the role of oxidative stress in the pathogenesis of OSMF and initiation and progression of carcinogenesis. Thus, it can be used as a prognostic marker for early detection of carcinoma in patients with OSMF and thereby, improving the quality of life patients.

A systematic review on the mechanisms of malignant transformation of oral submucous fibrosis.

Oral submucous fibrosis (OSMF), the most commonly encountered potentially premalignant oral epithelial lesion, is a chronic disorder associated with areca nut chewing. It has a relatively high potential for malignant transformation resulting into oral squamous cell carcinoma (OSCC), the most common oral malignancy with high mortality rate. Paymaster first described the malignant potential of OSMF in 1956, the rate of which had been estimated to be 7-13%. The pathogenesis of OSMF in itself is quite varied, and hence, its transformation to malignancy is also open to many varied mechanisms. The early diagnosis and sequentially, early treatment of OSMF is desirable so that the progression towards malignancy can be controlled. There are various theories that have been put forward explaining the probable pathway of malignant transformation of OSMF such as hypoxia, areca nut as a carcinogen or epithelial-mesenchymal transitions. Many recent molecular advances have also highlighted few biomarkers and genes that play a pivotal role in transformation of OSMF to OSCC. The purpose of this systematic review is to discuss all the possible mechanisms of malignant transformation of OSMF. Further research is still needed to establish the exact mechanism responsible for transformation of OSMF to OSCC and to reduce the mortality by newer interventions.

Computational analysis of p63+ nuclei distribution pattern by graph theoretic approach in an oral pre-cancer (sub-mucous fibrosis)

Background: Oral submucous fibrosis (OSF) is a pre-cancerous condition with features of chronic, inflammatory and progressive sub-epithelial fibrotic disorder of the buccal mucosa. In this study, malignant potentiality of OSF has been assessed by quantification of immunohistochemical expression of epithelial prime regulator-p63 molecule in correlation to its malignant (oral squamous cell carcinoma [OSCC] and normal counterpart [normal oral mucosa [NOM]). Attributes of spatial extent and distribution of p63+ expression in the epithelium have been investigated. Further, a correlated assessment of histopathological attributes inferred from H&E staining and their mathematical counterparts (molecular pathology of p63) have been proposed. The suggested analytical framework envisaged standardization of the immunohistochemistry evaluation procedure for the molecular marker, using computer-aided image analysis, toward enhancing its prognostic value. Subjects and Methods: In histopathologically confirmed OSF, OSCC and NOM tissue sections, p63+ nuclei were localized and segmented by identifying regional maxima in plateau-like intensity spatial profiles of nuclei. The clustered nuclei were localized and segmented by identifying concave points in the morphometry and by marker-controlled watersheds. Voronoi tessellations were constructed around nuclei centroids and mean values of spatial-relation metrics such as tessellation area, tessellation perimeter, roundness factor and disorder of the area were extracted. Morphology and extent of expression are characterized by area, diameter, perimeter, compactness, eccentricity and density, fraction of p63+ expression and expression distance of p63+ nuclei. Results: Correlative framework between histopathological features characterizing malignant potentiality and their quantitative p63 counterparts was developed. Statistical analyses of mathematical trends were evaluated between different biologically relevant combinations: (i) NOM to oral submucous fibrosis without dysplasia (OSFWT) (ii) NOM to oral submucous fibrosis with dysplasia (OSFWD) (iii) OSFWT-OSFWD (iv) OSFWD-OSCC. Significant histopathogical correlates and their corroborative mathematical features, inferred from p63 staining, were also investigated into. Conclusion: Quantitative assessment and correlative analysis identified mathematical features related to hyperplasia, cellular stratification, differentiation and maturation, shape and size, nuclear crowding and nucleocytoplasmic ratio. It is envisaged that this approach for analyzing the p63 expression and its distribution pattern may help to establish it as a quantitative bio-marker to predict the malignant potentiality and progression. The proposed work would be a value addition to the gold standard by incorporating an observer-independent framework for the associated molecular pathology.

Polymorphisms in the apoptosis-associated genes FAS and FASL and risk of oral cancer and malignant potential of oral premalignant lesions in a Taiwanese population

Our aim was to measure the relationship of FAS (-1377G>A and -670A>G), FASL (-844C>T) gene variants and risk of oral cancer. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to determine the FAS and FASL polymorphisms in 294 oral squamous cell carcinoma (OSCC), 53 oral submucous fibrosis (OSF), and 84 oral leukoplakia (OL) patients, as well as in 333 healthy controls. A standardized questionnaire was applied to collect demographic data, and potential confounding factors. JMP statistical software was used to analyze the association. FAS and FASL polymorphisms were not correlated with OSCC development or the malignant potential of OL by simple and multivariate logistic regression. However, a two- to fourfold difference in the risks of betel quid chewing, alcohol consumption, and smoking on OSCC development were observed between participants with different FAS polymorphisms. FAS polymorphisms were significantly correlated with the malignant potential of OSF. Multivariate logistic regression analysis indicated that FAS A(-1377)-G(-670) vs. G(-1377)-A(-670) haplotype (OR = 2.26, 95% CI = 1.16-4.41) was correlated with the malignant potential of OSF. We suggest that FAS and FASL polymorphisms are not significantly correlated with OSCC development or malignant potential of OL. The impact of substance usage on OSCC development could be differentiated by FAS polymorphisms. FAS A(-1377)-G(-670) haplotype may play a role in the malignant potential of OSF.