Grades Of Oral Submucous Fibrosis Research Articles

Correlation between transforming growth factor-beta expression and mast cell count in different grades of oral submucous fibrosis

Correlation between transforming growth factor-beta expression and mast cell count in different grades of oral submucous fibrosis

Assessment of collagen and elastic fibres in various stages of oral submucous fibrosis using Masson's trichrome, Verhoeff vangieson and picrosirius staining under light and polarizing microscopy

Background: Oral Submucous Fibrosis (OSMF) is a collagen related disorder seen in habitual betel-quid chewers. This is a high risk precancerous condition which clinically presents vertical palpable fibrous bands in buccal mucosa, generalized fibrosis of oral soft tissues with restricted mouth opening. Present study was undertaken to ascertain the changes occurring in collagen type I & III and elastic fibres in OSMF in relation to orientation, density and thickness. Study Methods: The study was performed on 15 cases in each group such as Stage I OSMF, Stage II OSMF, Stage III OSMF and normal oral mucosa (NOM). The biopsied samples were routinely processed for paraffin embedding; stained with Hematoxylin and Eosin as well as special stains like Masson's Trichrome (MT), Verhoeff Van Gieson (VVG) and Picrosirius red (PSR) and examined under light and polarized microscope respectively. MT stain demonstrated all types of collagen fibers collectively while PSR stain under polarized microscopy demonstrated collagen type I and type III separately with enhanced birefringence. VVG stain demonstrated very fine black colored elastic fibers, thus changes taken place could be accurately ascertained with progression of the disease. Results: Change in the orientation of collagen type I has been observed in stage II and stage III of OSMF from haphazard to parallel in relation to surface epithelium, while no change was noted in type III collagen fibres as well as elastic fibres in any stage of OSMF, and remained haphazardly arranged. Increased density of type I collagen was observed with increasing stage of OSMF from moderately dense to dense, while decrease in density of type III collagen was noticed in stage III than in stage II OSMF from moderately dense to sparse. The density of elastic fibres was decreasing from dense in stage I to sparse in stage III. Thickness of collagen type I was increasing with increasing grades while type III collagen and elastic fibres remained unchanged. Conclusion: The alterations in orientation, density and thickness of collagen fibres and density of elastic fibres in various grades of OSMF contribute to the clinical presentation of trismus with progression of the disease. Key Words: Collagen type I, Collagen type III, Elastic fibres, Masson's trichrome stain, Verhoeff Van Gieson stain, Picrosirius red stain

Aggrandizing oral submucous fibrosis grading using an adjunct special stain: A pilot study.

Introduction:Oral submucous fibrosis (OSMF) is graded according to various histological factors which include the epithelial changes and the connective tissue changes. These features though could be identified in routine hematoxylin and eosin (H and E) staining; they could be better appreciated in special stains. This pilot study is an attempt to identify a single special stain that can act as an adjunct to H and E stain to help grade this potentially malignant disease.Aims and Objectives:To assess if special stains can improvise on differentiating the various histological changes seen in OSMF and to accordingly grade OSMF cases.Materials and Methods:Formalin-fixed paraffin-embedded tissue sections of OSMF-10 cases of each grade (n = 30). Three special stains: Van-Gieson, Mallory's trichrome and Masson trichrome.Statistical Analysis:The results obtained were tabulated and statistically analyzed using Chi-square test.Observations and Results:The thickness and degree of keratinization were best detected in Mallory's stain (100%) and were statistically significant; the subepithelial changes were better detected using special stains, especially Mallory's stain (100%). The changes in collagen fibers were better visualized in all three special stains but were not statistically significant. The changes in blood vessels were better detected in Van-Gieson's and Mallory's stain; the obtained results were statistically significant. The degree of fibrosis between muscle bundles could be detected in all the three special stains, but when compared the results were not statistically significant. The questionable areas of muscle degeneration, especially in deeper connective tissue were better detected in Mallory's (43%) and Masson's stain (43%) as compared to Van-Gieson stain (14%) and the results obtained were statistically significant. The inflammatory cells and dysplastic features are better visualized in routine H and E stains.Conclusion:Pathogenesis of OSMF is related to fibro-elastic and muscle degenerative changes in the connective tissue followed by secondary changes in epithelium. Routine H and E, stains all the connective tissue components in various shades of pink, use of special stains bestows contrast between different components of connective tissue, thus improvising grading of OSMF. Mallory's stain can be used as a single adjunct to H and E stain as both pattern of keratinization in the epithelium and changes in the superficial and deeper connective tissue could be ascertained.

Association Between Grading of Oral Submucous Fibrosis With Frequency and Consumption of Areca Nut and Its Derivatives in a Wide Age Group: A Multi-centric Cross Sectional Study From Karachi, Pakistan.

Background:Oral submucous fibrosis (OSMF) is a chronic, premalignant condition of the oral mucosa and one of the commonest potentially malignant disorders amongst the Asian population. The objective of this study was to investigate the association of etiologic factors with: age, frequency, duration of consumption of areca nut and its derivatives, and the severity of clinical manifestations.Methods:A cross-sectional, multi centric study was conducted over 8 years on clinically diagnosed OSMF cases (n = 765) from both public and private tertiary care centers. Sample size was determined by World Health Organization sample size calculator. Consumption of areca nut in different forms, frequency of daily usage, years of chewing, degree of mouth opening and duration of the condition were recorded. Level of significance was kept at P ≤ 0.05.Results:A total of 765 patients of OSMF were examined, of whom 396 (51.8%) were male and 369 (48.2%) female with a mean age of 29.17 years. Mild OSMF was seen in 61 cases (8.0%), moderate OSMF in 353 (46.1%) and severe OSMF in 417 (54.5%) subjects. Areca nut and other derivatives were most frequently consumed and showed significant risk in the severity of OSMF (P ≤ 0.0001). Age of the sample and duration of chewing years were also significant (P = 0.012).Conclusions:The relative risk of OSMF increased with duration and frequency of areca nut consumption especially from an early age of onset.

Evaluation of matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2) in oral submucous fibrosis and their correlation with disease severity.

Oral submucous fibrosis (OSF), a potentially malignant oral lesion, is a form of pathological fibrosis affecting the oral mucosa. It results from an imbalance in equilibrium of the normal process of synthesis and degradation of extra cellular matrix. Matrix metalloproteinases and its inhibitors play important role in remodeling of the extra cellular matrix which are important in progression and pathogenesis of potentially malignant lesions to malignancy. To evaluate the expression and distribution of Matrix metalloproteinases-2 (MMP- 2) and Tissue inhibitor of metalloproteinases-2 (TIMP-2) in different grades of Oral Submucous Fibrosis(OSF). Immunohistochemical analysis for MMP-2 and its TIMP-2 was performed in 30 histopathologically confirmed, formalin fixed, paraffin embedded specimens of OSF. A semi-quantitative analysis was done to assess the expression, distribution and comparison of these in various stages of this disease. All moderately advanced cases and 64.2% for MMP-2 and 78.5% for TIMP-2 of early stage cases showed positivity. Between two stages of OSF, statistically significant differences were noted in expression of TIMP-2 in lamina propria, deep connective tissue and supra basal layers (p<0.05) and basal and supra basal layers for MMP-2 (p<0.05). The simultaneous increase in expression of MMP-2 and TIMP-2 with advancing stages of OSF can provide a basis for considering the proteases as important mediators in the pathogenesis and progression of OSF which could aid in identifying the aggressiveness of the condition and elucidate its role in its malignant transformation.

Quantitative evaluation of micronuclei in oral squamous cell carcinoma and oral submucous fibrosis patients: a comparative study.

The forte of research today aims at determining genotoxic changes in human cells as rapidly as possible. Micronuclei estimation in exfoliated cells is an easy, noninvasive and a reliable method to monitor genotoxic changes due to various reasons in oral mucosal cells. To identify, quantify and compare micronuclei in exfoliated buccal mucosal cells of healthy, oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) participants. In the present study, buccal smears from the 60 participants (30 each of OSMF and OSCC) and 30 age and sex matched controls were obtained and stained using Papanicolaou (PAP) staining method and observed under 100X magnification to identify and quantify micronuclei in the exfoliated cells of oral mucosa. There was a significant increase in micronuclei count from control to OSMF to OSCC. Also, a significant increase in the micronuclei frequency is observed with the different clinical stages and histological grades of OSMF and different histological grades of OSCC. Micronucleus assay can be used as an easy and consistent marker for genotoxic evaluation in higher risk groups and can be used for better treatment evaluation and prognosis in cases of OSMF and OSCC. Some relevant patents are also outlined in this article.

Estimation of argyrophilic nucleolar organizer regions in different grades of oral submucous fibrosis.

Context:Assessment of potential for malignant transformation of oral submucous fibrosis (OSF) through clinical or light microscopic examination of hematoxylin and eosin stained tissue sections is not totally satisfactory. The search is for such a tissue marker that will differentiate those cases of OSF, which carry a higher risk for malignant transformation. During the past few years, numerous workers have validated the usefulness of enumerating argyrophilic nucleolar organizer regions (AgNORs) in predicting the malignant potential of lesions. The present study was carried out to validate the diagnostic potential of this marker.Objectives of the Study:Quantitative and qualitative assessment of AgNORs in different grades of OSF and to compare the count of AgNORs in different grades of OSF and normal mucosa.Materials and Methods:AgNORs were investigated in tissue specimens from 90 patients diagnosed with different histopathological grades of OSF. AgNORs were identified in tissue specimens stained with silver nitrate, using light microscope. AgNORs were counted as small, large and total count to analyze them both quantitatively and qualitatively.Statistical Analysis Used:Results were subjected to statistical analysis for obtaining significance value (P value) by unpaired Student's t-test.Results:The mean total count of AgNORs was 2.464 ± 0.101, 4.358 ± 0.108, 3.704 ± 0.106 and 3.279 ± 0.161 in normal mucosa, Grades I, II and III of OSF, respectively. A qualitative difference was observed in the presentation of AgNORs in different grades of OSF. Mean value of small nucleolar organizer regions (NORs) decreased while the mean of large NORs increased as the grade of OSF increased.Conclusions:The study findings suggest that AgNORs are increased in OSF and they can serve as a reliable tool adjunct to histopathological diagnosis. Their ease of demonstration and high specificity to cellular proliferation make them the best available histopathological marker in the arsenal of an oral pathologist.

Expression of type I and type III collagens in oral submucous fibrosis: An immunohistochemical study

Background: Oral submucous fibrosis (OSMF) is a potentially malignant collagen - metabolic disorder linked to consumption of betel quid and areca nut. The deposition of collagen and its major subtypes have been the subject of intense scrutiny in the etiopathogenesis of the disorder. Aims and Objectives: The present study was planned to immunohistochemically identify the expression of collagens I and III (COL I and III) in different grades of OSF and compare it with normal oral mucosa and scar tissue. Materials and Methods: Archival paraffin sections of 72 cases of various grades of OSMF, ten cases of normal mucosa as controls and four cases of scar tissue were stained with antibodies to COL I and III (BioGenex Laboratories, CA, USA) to evaluate the collagen subtypes on paraffin sections. The expression was quantified by image analysis software (Jenoptik Optical System, ProgRes ® Capture Pro, version 2.8.8) and statistically analyzed. Results: COL I and III stained all the tissues ubiquitously. COL I was more in ratio and quantity in all the grades of OSMF, normal mucosa, and scar tissue. The proportion of COL I to COL III seemed to increase with progressive grades of OSF. Interestingly, during the process of fibrosis COL III seems to be deposited earlier and gradually replaced by COL I resulting in a skewed ratio vis a vis normal oral mucosa and scar tissue. Conclusions: COL I expression was found to be proportionate with advancing grades of OSF while COL III expression increased in Grade I but subsequently decreased as severity of OSF increased. The increase in COL I at the expense of COL III showed a similar pattern in the submucosa while in the deeper muscle only Grade III cases reflected the trend. While all cases of OSF revealed excessive expression in comparison with normal oral mucosa, the comparison with scar tissue was variable.

Correlation of areca habit, clinical grading, anorexia, and fatique in oral submucous fibrosis

Aim: The aim was to correlate the habit index (HI), clinical grading with anorexia, and fatigue in oral submucous fibrosis (OSMF). Settings and Design: Hospital-based study including a total of 60 individuals, out of which 30 patients were with OSMF, (27 males and 3 females). A group of 30 individuals, with areca chewing habit but without any oral lesions were selected as a control group. Subjects and Methods: Detailed case history was recorded. Height and weight measurements were made to assess body mass index (BMI). Fatigue and anorexia scores were calculated using structured questionnaires. Clinical staging of OSMF was done according to Khanna JN and Andrade NN (1995) classification. The information related to the type of habit, site of placement of areca nut, and duration was recorded using HI. Statistical Analysis Used: Statistical analysis was done using Pearson's correlation and Student's t-test. Results: A statistically significant difference was found between anorexia in both the groups (P = 0.01) and a highly significant difference was seen in HI (P = 0.001). However, the comparison between other parameters was found to be statistically not significant. The correlation of HI, anorexia, and fatigue score in Grade I, Grade II, Grade III, and Grade IV OSMF within each group was not significant statistically. However, in Grade IV a strong correlation was found between BMI and anorexia score (P = 0.0188). Conclusion: The merits of this study include a positive correlation between anorexia and fatigue with disease progression and a congruent relation of HI with the grades of OSMF.

Immunohistochemical analysis of tenascin expression in different grades of oral submucous fibrosis.

Aim:Tenascin, a glycoprotein, is one of the major constituents of extracellular matrix, which may function in organizing the stroma in normal and pathological conditions. The study aimed to correlate the structural organization of tenascin with the pathological progression of disease from early, moderate and advanced changes in oral submucous fibrosis (OSMF).Study Design:A retrospective cross-sectional immunohistochemical (IHC) analysis of OSMF cases was performed. Total 70 slide samples were prepared for the study from 35 formalin-fixed paraffin-embedded tissue blocks with 10 each from histologically proven and graded as early, moderate and advanced OSMF and 5 of normal oral mucosa. The IHC sections were analyzed for the intensity and pattern of tenascin expression at the junction of epithelium and connective tissue (ECJ) and deeper connective tissue (CT), as well as presence or absence of staining around inflammatory cells, fibroblast and endothelial cells using anti-human tenascin.Result:Most of the OSMF cases showed retention of antigen at ECJ and in deeper CT. Its expression varied in different grades as well as around inflammatory cells, fibroblast and endothelial cells in same tissue section. Highly significant P values of 0.001 and 0.003 were obtained for tenascin intensity and pattern, respectively, at ECJ in different OSMF grades. In addition, for the expression of tenascin pattern in deeper CT among different OSMF grades, a significant P value of 0.018 was obtained.Conclusion:A differential expression of tenascin was observed with the progression of disease. The expression of tenascin as bright and continuous deposition at ECJ in early and moderate stages of OSMF signifies either proliferative organization within the overlying epithelium or an epithelial-mesenchymal interaction. However, a weak immunoreactivity of tenascin at ECJ was observed in advanced stage of OSMF.

Pleomorphism of argyrophilic nucleolar organizer regions in oral submucous fibrosis and oral squamous cell carcinoma.

Background:Argyrophilic nucleolar organizer regions (AgNORs) is demonstrated to be useful in diagnostic pathology, mainly to distinguish benign lesions from their malignant counterparts. We aimed to correlate AgNORs pleomorphism with the severity of lesion in oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) using a retrospective study on 45 archival tissues.Materials and Methods:Silver nitrate staining was performed on archival tissues consisting of 20 OSMF and 20 OSCC. Five biopsies from normal oral mucosa acted as a control. One hundred cells per slide were observed for AgNORs dots, which were classified as typical (spherical) and atypical (large, kidney-shaped and clustered).Results:A positive and significant correlation was found between increased atypical shapes and increasing grades of OSMF and OSCC.Conclusions:AgNORs pleomorphism can be a reliable criterion to assess disease severity and progression in OSMF and OSCC.

Assessment of tissue copper level in oral submucous fibrosis patients

Background: Oral submucous fibrosis (OSMF) is a precancerous condition with a high risk (7.6%) of cancer development. It is caused by use of areca nut in various forms. Areca nut contains high level of copper as compared to other commonly eaten nuts. Copper acts as cofactor of lysyl oxidase (LOX) that controls maturation of collagen. Aims: The aim of the study is to estimate tissue copper level in OSMF patients with habit of areca nut chewing and to correlate any change in tissue copper level with histopathological grading of OSMF. Materials and Methods: A hospital based case-control study was done on 30 subjects visiting out-patient department (OPD) of Kothiwal Dental College Moradabad, of which 15 were clinically diagnosed OSMF cases with habit of areca nut chewing and 15 were taken as controls with no habit of areca nut chewing. Tissue copper levels were measured by Atomic Absorption Spectrophotometer (AAS). Results : The study showed highly significant difference in mean tissue copper level (P P Conclusions : The present study confirms the hypothesis that copper level in increased in areca nut chewers presenting OSMF. Moreover, copper level increased with increased in histopathological grade of OSMF.

Evaluation of plasma fibrinogen degradation products and total serum protein concentration in oral submucous fibrosis.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder with a multifactorial etiology. Malnutrition is a major problem for the inhabitants of most countries where OSMF is prevalent. Recently, a new direction in the etiopathogenesis was provided by the identification of fibrinogen degradation products (FDP) in the plasma of OSMF patients. To assess the role of FDP in the etiology of OSMF and to correlate with the nutritional status by evaluating the total serum protein level. The study also determines to evaluate the correlation between the levels of plasma FDP with respect to the staging and grading of OSMF. Correlation between the levels of Total Serum Protein (TSP) with respect to the staging and grading of OSMF was also evaluated. The study included 30 cases clinically and histopathologically diagnosed as oral submucous fibrosis. The FDP levels were assessed using both qualitative and semi quantitative method as supplied by 'Tulip Diagnostics (P) Ltd. Total Serum Protein (TSP) estimation was done by Biuret method using Liquixx Protein kit by Erba, Manheim. The study indicates that in qualitative assessment of FDP only 14 subjects showed the presence of FDP levels>200ng/ml. In semiquantitative assessment there is no significant association between varying clinical stages and histopathological grades and FDP levels. Total serum Protein level showed a marginal increase in all subjects. The study revealed a positive correlation between FDP and TSP in all OSMF subjects. A larger sample size which would be a better representation of the population and the use of different methods which have higher sensitivities and specificities to evaluate FDP level and detailed fractional analysis of protein along with immunoglobulin profiling would facilitate in attaining more conclusive results.

Transforming growth factor β2 (TGF-β2) in pathogenesis of oral submucous fibrosis: An immunohistochemical study

Background and Objectives: Oral Submucous Fibrosis (OSF) is a potentially malignant oral disorder causing fibrosis of the oral mucosa. Commonly associated with the habit of chewing areca nut in its raw or refined forms, the progressive fibrosis causes intense debility and probable malignant transformation. Arecoline, flavinoids and tannins in the areca nut may activate pro-fibrotic cytokines like transforming growth factor beta (TGF-β) leading to fibrosis. TGF-β and its isoforms probably represent the major pathway in the deposition of collagen fibers in this condition. Very little is known of the role of TGF-β2, as compared withTGF-β1, in OSF. The present study aims to evaluate TGF-β2 immunohistochemically in OSF with a view to understanding its role in the pathogenesis. Materials and Methods: TGF-β2 antibody was detected immunohistochemically on archival paraffin sections of 70 cases of various grades of OSF, 10 cases of normal oral mucosa and five cases of scar tissue. The presence and distribution of the antibody was noted and a quantification of the positive areas was also done using image analyses software and correlated in proportion to the rest of the tissue. Results: Expression of TGF-β2 was more in all grades of OSF when compared with that of normal oral mucosa but less than that expressed in scar tissue. The antibody was detected in epithelium, around the blood vessels, in areas of inflammatory infiltrate, fibroblasts and in muscles. The intensity and proportion of expression paralleled increasing grades of OSF. There was increased expression of the antibody in the epithelium, which is probably the source, but no correlation to epithelial changes (hyperplasia, atrophy or dysplasia) was noted. Conclusion: TGF-β2 is a prominent cytokine in the TGF-β induced pathway of fibrosis but probably plays a contributory role to the main isoform TGF-β1. Its role as a marker of malignant transformation, as seen in other systemic malignant lesions, remains inconclusive in OSF.

Transforming growth factor beta 1 in oral submucous fibrosis: An immunohistochemical study - Understanding the pathogenesis

Background: The development of fibrosis is pathognomic in the potentially malignant oral disorder, oral submucous fibrosis (OSF). Strong evidence exists to implicate the chewing of areca nut in the pathogenesis of the lesion. The constituents of areca nut activate several pro-fibrotic cytokines, chiefly transforming growth factor beta 1 (TGF-β1), which leads to an increased deposition and decreased degradation of extracellular matrix and collagen. TGF-β1 probably represents the major pathway in the deposition of collagen fibers in this condition. The present study aims to identify and correlate the expressions of TGF-β1 immunohistochemically on paraffin sections of various stages of OSF. Materials and Methods: The expression of TGF-β1 antibody was detected immunohistochemically using the anti-TGF-β1 mouse monoclonal antibodies (8A11-NovusBio USA) on paraffin sections of 58 cases of OSF, 10 cases of normal buccal mucosa tissue and 5 cases of scar tissue. The site, extent, and intensity of expression and quantification of TGF-β1 were noted and a comparative evaluation between various grades of OSF. Scar tissue and normal oral mucosa was made using image analysis software (Jenoptik optical system-ProReg ® Capture Pro 2.8.8 software [2011]). Results: Cells of spinous layer of the epithelium showed more intense staining in all grades of OSF, Grade II showed the highest percentage of expression, same as that of keloid (17%) but less than that of normal mucosa (12%). Positive staining was seen around blood vessels, muscles, fibers in the submucosa and perimuscle fibers. Highest expression was in the muscle in Grade III (80%) compared with normal oral mucosa (37%). Conclusion: These results suggest that the pathogenesis of OSF and scar/keloid could be linked through the TGF-β1 pathway. Interventions directed at the TGF-beta pathway may hold the key in the future management of this oral potentially malignant condition.

Proposed new grading of oral submucous fibrosis based on cheek flexibility.

Objectives: Oral submucous fibrosis (OSMF) is a potentially malignant disorder of oral cavity, pharynx and upper digestive tract, characterized by progressive inability to open the mouth. Based on clinical and/or histopathological features, various classifications and grading systems have been put forth till date. The aim of the present study was to study the variance in cheek flexibility in OSMF patients, the observance of which led to the introduction of a new grading for the condition. Material and Methods: The study included 412 patients with OSMF attending to the Department of Oral Medicine and Radiology during the period from December 2008 to June 2013. A detailed history and examination of the patients was performed with special emphasis on measuring cheek flexibility. Statistical analysis was done using Chi-square test and p<0.05 was considered to be statistically significant. Results: The most common etiological factor was tobacco (73.3%). All the patients reported with burning sensation of the mouth and blanching of the mucosa. Malignancy was reported in only 4.6% patients. 60.4% patients showed cheek flexibility of 30mm and above, while 29.6% patients showed cheek flexibility between 20-30mm and 10% patients showed less than 30mm of cheek flexibility. Conclusion: The observations of the present study have led to the proposal of a new grading of OSMF based on cheek flexibility which could assist in the categorization of the condition by the clinicians. Key words:Cheek flexibility, oral submucous fibrosis, grading, areca nut.

Does Clinical Staging and Histological Grading Show Parallelism In Oral Submucous Fibrosis? A Retrospective Study from an Indian City

Objectives: Oral submucous fibrosis is a common oral health problem in India. This study was conducted to correlate the histopathological diagnosis with habits and clinical findings in patients suffering from oral submucous fibrosis (OSF). Methods: The study group comprised of randomly included 40 patients. A comparison between clinical staging (a method used to find out the stage of disease using tests which include physical examination) and histopathological grading (grading is a measure of the cell appearance in pathology) was done in each case. Fisher’s exact test was done to obtain statistical analysis. Results: Among 15 cases of clinically diagnosed stage I lesions, 4 (10%) were grade I, 6 (15%) were grade II and 5 (12.5%) were grade III. Among 23 cases of stage II lesions 6 (15%) were diagnosed as grade I, 7 (17.5%) as grade II, 7 (17.5%) as grade III and 3 (7.5%) as grade IV. Among 2 cases of stage III both were diagnosed as grade II respectively. Conclusions: There was no correlation between clinical staging and histopathological grading of oral submucous fibrosis. The test results were statistically not significant. (p=0.635) This may be due to difference in severity and extent of fibrosis in different parts of the oral mucosa.

Immunohistochemical expression of CD34 and basic fibroblast growth factor (bFGF) in oral submucous fibrosis.

Background:Oral submucous fibrosis (OSMF) is an insidious chronic fibrotic condition that involves the oral mucosa and occasionally the pharynx and esophagus. Vascularity in OSMF has always been a matter of debate. The prevailing concept is that epithelial atrophy occurs due to lack of perfusion but the recent data challenges this concept. Therefore, the present study was conducted to evaluate the immunoreactivity of CD34 and basic fibroblast growth factor (bFGF) in different histological grades of OSMF. This might further shed light to the role of microvasculature in OSMF, so that the epithelial atrophy and resultant malignant transformation seen in the advanced stages might be elucidated.Materials and Methods:A total of 30 cases of OSMF were included in the study and mean vascular density (MVD) was calculated using CD34 and bFGF. Five cases of OSMF with dysplasia and 2 cases of OSMF turning malignant were added during the course of the study.Results:Mean vascular density was found to decrease significantly as the diseases advanced. Furthermore, vascularity increased significantly in cases of OSMF turning towards malignancy.Conclusion:Our study supports the concept of epithelial atrophy aftermath of lack of perfusion. There is reduced vascularity as the disease advances and this denies the systemic absorption of carcinogens, which affects the already compromised epithelium. Consequently, liberation of angiogenic factors occurs because of malignant transformation, which explains the neoangiogenesis and increased vascularity in OSMF turning towards malignancy. Further studies are required to identify the mechanism leading to carcinogenesis in the atrophied epithelium aftermath of fibrosis and decreased vascularity.

Immunohistochemical evaluation of myofibroblasts using alpha-smooth muscle actin in oral submucous fibrosis

Introduction: Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a premalignant condition of the oral cavity characterized by generalized submucosal fibrosis with a multifactorial etiology. Myofibroblasts are a unique group of cells phenotypically intermediate between smooth muscle cells and fibroblast exhibiting contractile properties, expressing α-smooth muscle actin (α-SMA) and are considered primary producers of extracellular matrix after injury. Their accumulation has been established as a marker of progressive fibrosis in various organs. The aim of the present study is to evaluate and compare the myofibroblasts in various histological grades of OSMF. Materials and Method: Fifteen cases of OSMF, which were further categorized histologically into early (5 cases), moderately advanced (5 cases) and advanced (5 cases), were subjected to immunohistochemical evaluation using α-SMA antibody for detection of myofibroblasts. Fifteen benign mucosal proliferation specimens were also stained for comparison. Results: The number of myofibroblasts in OSMF was significantly increased when compared to that of benign mucosal proliferations (P < 0.05). Additionally, a statistically significant increase in the myofibroblasts population between early and advanced stages was observed (P < 0.05). Conclusions: The results of the present study showed that expression of myofibroblasts within the OSMF group showed a progressive increase from the early OSMF through moderate OSMF and the advanced OSMF group indicating that myofibroblasts could serve as effective prognostic marker for disease progression in oral submucous fibrosis.

Plasma fibrinogen degradation products in betel nut chewers - with and without oral submucous fibrosis.

Context:Oral submucous fibrosis (OSMF) has a multifactorial etiology. Recent studies have shown that there is an increased level of fibrinogen degradation products (FDP) in plasma of OSMF patients suggesting its possible role in etiopathogenesis of OSMF.Aims:To detect the presence of FDP in the plasma of betel nut chewers with and without OSMF and in normal subjects without any habits, to correlate these levels with respect to the clinical and histological grading of OSMF and whether it can be used as a nonsurgical diagnostic aid in detection of suspected OSMF cases.Materials and Methods:Study comprised of 35 cases of betel nut chewers with OSMF, 10 patients with betel nut chewing habit but having apparently normal oral mucosa, and 10 normal patients without any habits. The patients were evaluated for plasma FDP levels.Results:All the betel nut chewers with OSMF showed the presence of plasma FDP. However, controls and subjects with habit, but without OSMF did not show FDP in the plasma. Spearman's rank correlation was used to find the association between the clinical and histological grades and it was not statistically significant (P = 0.910) and the correlation being 0.020.Conclusion:Since only those patients with OSMF have showed the presence of FDP in plasma, we suggest that our test can be utilized as a nonsurgical diagnostic aid in suspected OSMF patients.