Advanced Oral Submucous Fibrosis Research Articles

Novel role of CD34+ stromal cells/telocytes in oral submucous fibrosis development and its malignant transformation

BackgroundTelocytes are interstitial cells widely distributed in the extracellular matrix of numerous tissues distinguished by their long, thin, and moniliform projections. Telocytes have a role in the stimulation of angiogenesis and contribute to the development and progression of fibrosis. AimThe current study aimed to assess and compare the telocyte distribution in normal mucosa, oral submucous fibrosis (OSF), and OSCC associated with OSF (OSCCOSF). Materials and MethodsFormalin-fixed and paraffin-embedded tissue blocks of 30 OSF cases, 15 OSCCOSF cases, and 15 normal oral mucosae were obtained. Immunohistochemical staining was done with antibodies to CD34 to assess the vasculature and telocytes. The mean vascular density (MVD) and mean telocyte density were compared between the groups using the Kruskal-Walli test. ResultsA statistically significant high MVD (3.4 ± 1.22) and mean telocyte density (3.8 ± 1.35) was observed in OSCCOSF cases while it was lowest in advanced OSF cases. MVD was higher in early OSF cases than in normal mucosa. ConclusionThis study showed a decrease in CD34-positive telocytes in OSF, indicating that telocyte loss promotes the development of fibrosis.Increased angiogenesis coexisted with an increase in telocytes in OSCCOSF.

Evaluation of stromal myofibroblasts in oral submucous fibrosis and its malignant transformation: An immunohistochemical study.

Oral submucous fibrosis (OSF) is a precancerous lesion, with oral squamous cell carcinoma (OSCC) being the most prevalent malignancy affecting the oral mucosa. The malignant transformation of OSF into OSCC is estimated to occur in 7-13% of cases. Myofibroblasts (MFs) play pivotal roles in both physiological and pathological processes, such as wound healing and tumorigenesis, respectively. This study aimed to explore the involvement of MFs in the progression of OSF and its malignant transformation. In total, 94 formalin-fixed paraffin-embedded tissue blocks were collected, including normal oral mucosa (NOM; n = 10), early-moderate OSF (EMOSF; n = 29), advanced OSF (AOSF; n = 29), paracancerous OSF (POSF; n = 21), and OSCC (n = 5) samples. Alpha-smooth muscle actin was used for the immunohistochemical identification of MFs. NOM exhibited infrequent expression of MFs. A higher staining index of MFs was found in AOSF, followed by EMOSF and NOM. Additionally, a significant increase in the staining index of MFs was found from EMOSF to POSF and OSCC. The staining index of MFs in NOM, EMOSF, AOSF, POSF, and OSCC was 0.14 ± 0.2, 1.69 ± 1.4, 2.47 ± 1.2, 3.57 ± 2.6, and 8.86 ± 1.4, respectively. All results were statistically significant (P < 0.05). The expression of MFs exhibited a gradual increase as the disease progressed from mild to malignant transformation, indicating the contributory role of MFs in the fibrogenesis and potential tumorigenesis associated with OSF.

Force, alternate movements, snap, suction and vibration functions of tongue are altered in oral submucous fibrosis patients

BackgroundOne of the most common clinical manifestations of oral submucous fibrosis (OSMF) is restricted tongue movements. However, the characterization of involvement is needed to better understand the impairment of its functioning. In the present study, force, alternate movements, snap, suction, and vibration functions of the tongue were investigated in OSMF patients. MethodsA total of 53 OSMF and 40 healthy individuals were recruited in the present study. Clinical parameters were used for the diagnosis and grading of OSMF. Alternate movements, snap, suction, vibration of the tongue and tongue force were assessed using standard methodology. ResultsOut of 53 OSMF subjects, 22 (42%) were in early stages and 31 (58%) in late stages. There were statistically significant differences between the OSMF and healthy individuals for tongue functions such as protrusion, retraction, lateral movements, altered snap, suction, and tongue vibration (p < 0.00001). All of the aforementioned tongue functions were more affected in advanced stage OSMF than in early stage OSMF (p < 0.00001). ConclusionForce, alternate movements, snap, suction and vibration functions of tongue are significantly altered in OSMF patients. The performance of the tongue movements by the OSMF subjects worsened with the disease progression.

Expression and correlation of the Pi3k/Akt pathway and VEGF in oral submucous fibrosis.

Oral submucous fibrosis (OSF) has a high incidence in Asia countries, but its underlying molecular mechanism was not exploited completely. In this research, we investigated the expression of the phosphatidyl inositol 3-kinase (Pi3k)/protein kinase B (Akt) pathway and vascular endothelial growth factor (VEGF) in oral submucosal fibrosis, explore the correlation between the Pi3k/Akt pathway and VEGF, and identify the mechanisms involved in OSF. The pathological changes and fibrosis stages of OSF tissues (n = 30, 10 each of early, moderate and advanced OSF) were determined using Haematoxylin-eosin staining (HE) and Masson staining, respectively. Collagen type I (Col-I), Pi3k, Akt, VEGF, TGF-β and p-Akt expression was detected using immunohistochemistry, qPCR and WB. The correlation between Pi3k, Akt and VEGF was analysed. Col-I expression increased as OSF progressed. However, their expression was downregulated in normal and moderate to advanced OSF tissues. VEGF expression positively correlated with Pi3k and Akt expression. VEGF expression correlated positively and negatively with the Pi3k inhibitor, LY294002 below and above a concentration of 10 μM, respectively. VEGF expression correlated positively with the Pi3k/Ak activator, IGF-1. Due to the synergistic effect between Pi3k/Akt pathway and VEGF on OSF lesions and fibrosis process, targeted Pi3k/Akt pathway regulation can induce VEGF expression and improve ischemia, ultimately treating OSF.

Evaluation of extracellular matrix changes among oral submucous fibrosis and oral squamous cell carcinoma patients of Malwa region of Punjab using special histochemical stains: An insight into cancerous transformation.

To assess extracellular matrix changes among oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) patients using special histochemical stains. Twenty biopsy specimens of OSMF and 30 biopsy specimens of OSCC were included in the present study. Among 20 OSMF specimens, 10 were of early OSMF and the remaining 10 were of advanced OSMF. Out of 30 OSCC specimens, 10 cases each were of well-differentiated OSCC, moderately differentiated OSCC and poorly differentiated OSCC. Three sections, each 4 μm thick, were obtained from all specimens. One section was stained with routine H&E staining, whereas the other section was stained with Masson's trichrome (MT) stain for collagen and Verhoeff-Van Gieson (VVG) for elastic fibres. Evaluation of all specimens was performed under the light microscope. The arrangement of collagen fibres and elastic fibres was compared between the OSMF group and OSCC group, in between different grades of OSMF and in between different grades of OSCC. The results were evaluated using SPSS software. Early OSMF cases were associated with fibrosis in the superficial lamina propria, whereas advanced OSMF had fibrosis involving deeper muscle fibres. In all early OSMF cases, elastic fibres were arranged in thin bundles, whereas in advanced OSMF cases, elastic fibres were in thick bundles. In well- and moderately differentiated OSCCs, the collagen fibres were arranged in thick bundles and in poorly-differentiated OSCCs, the collagen fibres appeared to be fragmented. The elastic fibres in well-differentiated OSCC and moderately-differentiated OSCC were thickly arranged, and poorly-differentiated OSCC showed thin fibres and 70% of cases showed the absence of elastic fibres. Changes observed in both collagen and elastic fibres in the extracellular matrix (ECM) can be taken as a study model to further understand the progression of OSMF to OSCC using histochemical stains.

Assessment of Oral Lesions With Tobacco Usage: A Cross-Sectional Clinicopathological Study in Sri Ganganagar, Rajasthan, India.

Background Tobacco usage in the form of smoking or chewing has increased the risk of oralpotentiallymalignant disorders (OPMDs) and oral cancer. These deleterious habits are also related to changes in dentition and the oral mucosa. Aim The aim of our study was to evaluate the oral changes associated with tobacco usage among residents of Sri Ganganagar. Materials and methods This study was conducted among the residents of Sri Ganganagar, Rajasthan, India, using stratified cluster random sampling, prestructured questionnaires, and detailed oral examination. A total of 100 patients with a previous history of tobacco usage were enrolled in this study after obtaining informed consent. Age- and gender-matched controls were also evaluated to correlate the findings. Clinical details were documented, including the Oral Hygiene Index-Simplified (OHI-S), Decayed-Missing-Filled Teeth (DMFT) index, Community Periodontal Index (CPI), loss of attachment, dental findings, and oral mucosal changes. Suspicious lesions were stained with toluidine blue, and a biopsy was performed for histopathological evaluation. The tabulated results were statistically analyzed using theStatistical Package for the Social Sciences (SPSS) version 21.0 (IBM SPSS Statistics, Armonk, NY, USA)for significance. Results Attrition, abrasion, and erosion of teeth were more frequent in tobacco users than in controls. Smoker's palate, tobacco pouch keratosis, and leukoplakia were commonly noted mucosal lesions. The mean values of the parameters of the DMFT score (3.560), CPI score (2.190), and loss of attachment score (0.542) were higher among tobacco users, and it was statistically significant (P value < 0.05). Out of 100 patients, 17 had suspicious lesions. It included seven cases of oral submucous fibrosis (OSMF), two cases of tobacco pouch keratosis, and eight cases of leukoplakia. Toluidine blue staining and biopsy were performed. Histopathological examination of suspicious lesions revealed hyperkeratosis, various grades of epithelial dysplasia, and differing inflammatory responses. Out of 17 biopsied cases, there were two cases of hyperkeratosis with severe epithelial dysplasia, four cases of hyperkeratosis with moderate epithelial dysplasia, two cases of hyperkeratosis with mild dysplasia, two cases of superficially invasive squamous cell carcinoma, five cases of advanced OSMF, and two cases of moderately advanced OSMF. Conclusion Tobacco usage produces visible changes in dentition and latent alterations in the oral mucosa. Suspicious lesions should always be referred for histopathological examination to identify oral potentially malignant disorders and oral cancerso that prompt treatment could be initiated. Patient education is mandatory to avoid the usage of tobacco in any form.

Assessment of Changes in Birefringence and Orientation of Collagen Fibres in Different Grades of Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma using Picrosirius Red and Polarising Microscopy

Introduction: Oral submucous fibrosis (OSMF) is a potentially malignant disease with a prevalence of 7-13%. It is characterised by the fibroelastic changes due to excessive deposition of collagen which results in dense fibrous bands and epithelial changes. About 90-95% of oral cancers are Oral Squamous Cell Carcinoma (OSCC). Stroma produced by the invading neoplastic cells are rich in collagen fibres. These collagen fibers have been the main focus of study to understand the pathogenesis of these lesions. Hence, these fibres have been evaluated under polarised microscopy following staining with Picrosirius red stain. Aim: To evaluate changes in birefringence, thickness and orientation of collagen fibres in different histopathological stages of OSMF and OSCC. Materials and Methods: This observational study involved sections of clinically and histopathologically confirmed cases of OSCC and OSMF from Department of Oral Pathology and Microbiology, Rajarajeswari Dental College and Hospital, Bangalore. The study was conducted for a duration of one year from April 2017 to March 2018. The study included total 60 cases among which 20 for each-normal mucosa, OSCC and OSMF. Tissue sections were stained with Picrosirius red stain and collagen fibres were analysed for colour, thickness and orientation under polarised microscope. Chi-square test was used for statistical analysis. Significance was set at p-value &lt;0.05. Results: Comparison of birefringence of collagen fibres between OSMF, OSCC and normal mucosa was not statistically significant (p-value=0.37). Orientation of collagen fibres between OSMF, OSCC and normal mucosa was statistically significant with (p-value=0.02). Conclusion: This study showed a change in colour from yellow orange to orange red in advanced OSMF cases which indicated progression of disease and tightly packing of collagen fibres, suggestive of presence of thick fibres in the extracellular matrix. In OSCC, the colour change from yellow orange to orange red and haphazardly arranged collagen fibres was indicative of transformation of preneoplastic to carcinoma stage.

A Histopathology-based Assessment of Biological Behavior in Oral Hyalinizing Extraosseous Lesions by Differential Stains

The assessment of hyalinization to determine aggressive behavior in oral pathological lesions is a scarcely researched field that requires further exploration. The current study aims to predict the biological behavior of oral hyalinizing extraosseous lesions (OHEOL) by employing four differential stains with clinicopathologic correlation. The study was performed on retrospectively diagnosed formalin-fixed paraffin-embedded cases of salivary gland tumors (SGTs) (n = 13), benign soft tissue (BST) lesions (n = 24), and oral submucous fibrosis (OSMF) (n = 53). The hematoxylin and eosin-stained sections were analyzed for the severity of hyalinization (SOH). Differential stains periodic acid Schiff (PAS), Alcian blue, safranin O, and picrosirius red with polarizing microscopy were used to assess the components of hyalinized tissue. The SOH was correlated with differential staining characteristics and clinicopathologic features to analyze possible correlation with aggressive potential in BST, advancement of disease in OSMF, and recurrence in SGT. Intensity of picrosirius red stain significantly correlated with SOH of SGTs (p = 0.044). The intensity of PAS stain (p = 0.040), picrosirius red polarizing greenish-yellow color (p = 0.002), and pattern of distribution of picrosirius red (p = 0.023) significantly correlated with recurrence of SGTs. The intensity of differential stains increased with the SOH in BST lesions indicating their correlation with SOH. The intensity (p = 0.008) and pattern (p = 0.010) of Alcian blue staining and intensity of safranin O stain (p = 0.003) significantly correlated with SOH in OSMF. Picrosirius red polarizing color reddish and yellowish red (p = 0.002) significantly correlated with SOH distinguishing early and advanced OSMF. Picrosirius red and PAS stains are reliable indicators of SOH and recurrence potential in SGT. Alcian blue, safranin O, and picrosirius red polarizing colors enable detection of SOH and accurately distinguish early from advanced OSMF. SOH can be considered as a histological predictor of aggressive biologic behavior in OHEOL. These findings will result in appropriate management protocols.

Evaluation of muscle involvement &amp; degeneration in advanced oral submucous fibrosis using three different stains – a retrospective cross-sectional study

ABSTRACT Background: Oral submucous fibrosis (OSMF) is graded according to various histological factors which include the epithelial changes and the connective tissue changes. These features could be identified in routine Hematoxylin and Eosin (H and E) staining in shades of pink. However, the use of special stains provides a contrast to various connective tissue components thereby aiding in better visualization of these connective tissue changes in advanced OSMF cases. Objective: To compare and evaluate muscle involvement and degeneration in advanced oral submucous fibrosis using three different stains namely, H&amp;E, Van Gieson, and Masson’s Trichrome. Material and Methods: 10 Formalin-fixed paraffin-embedded tissue sections of advanced OSMFwere stained using 3 different stains namely Hematoxylin and Eosin (H&amp;E), Van-Gieson, and Masson trichrome. The results obtained were tabulated and statistically analyzed using Kruskal Wallis ANOVA. Results: The hyalinization and fibrosis involving the skeletal muscle were better visualized in Masson’s Trichrome but were not statistically significant. The muscle degeneration in deeper areas was better visualized in Masson’s trichrome when compared to the H&amp;E and Van Gieson. Conclusion: Hematoxylin and eosin 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. Masson’s trichrome stain can be used as a single adjunct to hematoxylin and eosin stain as changes in the superficial and deeper connective tissue could be ascertained. Keywords Fibrosis; Masson’s trichrome stain; Muscle degeneration; Oral submucous fibrosis grading.

Role of programmed cell death 4 in myofibroblast differentiation in oral submucous fibrosis.

Background:Fibrosis is an uncontrolled healing process, led by persistent differentiation of fibroblast to alpha-smooth muscle actin (αSMA) positive activated fibroblast or myofibroblast. Oral submucous fibrosis (OSMF) is one such condition that is associated with areca nut use. Recently, Programmed Cell Death 4 (PDCD4), a pro-apoptotic marker, has been shown to modulate fibroblast differentiation in various organ fibrosis. The present study aimed to evaluate the role of PDCD4 in the regulation of fibroblast differentiation in OSMF.Materials and Methods:Paraffin-embedded tissue sections from 45 cases of the normal oral mucosa, early OSMF and advanced OSMF were examined for PDCD4 and αSMA expression by immunostaining. Co-expression of PDCD4 and αSMA in fibroblasts was examined using Spearman's correlation test.Results:The stromal fibroblasts showed minimal expression of αSMA in the normal mucosa and early OSMF, while advanced OSMF groups demonstrated a higher frequency of αSMA myofibroblasts. The PDCD4 expression was noted in the normal stromal fibroblasts. However, this expression appeared to progressively reduce with an increasing grade of OSMF. Thus, a negative correlation was noted between stromal PDCD4 and αSMA expression with progressive OSMF.Conclusion:This study demonstrated a putative role for PDCD4 in oral fibrosis consistent with its role in other tissues. The lack of PDCD4 expression with increasing myofibroblast expression in OSMF suggests that targeting its dysregulation may be an attractive translational therapeutic target.

Expression of p63 and Proliferating Cell Nuclear Antigen in Oral Submucous Fibrosis.

ABSTRACTAim:Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant disorders such as oral submucous fibrosis (OSMF). p63 can detect genetic changes in OSMF and it facilitates early detection of malignant transformation, whereas proliferating cell nuclear antigen (PCNA) is a marker of proliferation and may prove to be a useful objective indicator of the biological behavior of various tumors. The aim of this study was to investigate the expression and pattern of the intensity of p63 protein and PCNA in normal oral mucosa and OSMF using immunohistochemistry (IHC) and to correlate the expression of these biomarkers.Materials and Methods:A total of 15 archival paraffin-embedded blocks obtained from our department, which were histopathologically diagnosed early OSMF (n = 4), intermediate OSMF (n = 4), and advanced OSMF (n = 2) and normal mucosa (n = 5), were taken as the standard for comparison. p63 and PCNA positivity was analyzed using Kruskall-Wallis test followed by pairwise comparison using Mann-Whitney U test. The pattern of staining and intensity was compared using Chi-Square test for which Statistical Package for the Social Sciences (SPSS, v 22.0, IBM Corporation, Armonk, New York) was used.Results:All samples showed positive staining for p63 and PCNA. A statistically significant difference (P < 0.05) was seen between the frequency of occurrence of p63 and the PCNA pattern of expression among all the groups. The intensity of staining was mild to intense in the basal layer, as there was a progression toward the severity of the disease. Almost 75.4% correlation existed between p63 and PCNA, with high correlation and marked relationship.Conclusions:The OSMF is considered a potentially malignant disorder that has the potential to get transformed into OSCC. The malignant transformation is often associated with changes at the genetic level, and these are reflected by the altered expression of proteins. Our results showed that biomarkers such as p63 and PCNA are significant in predicting the malignant transformation in OSMF, so in future they may serve as a prognostic tool in the early detection of malignancies.

Surgical management of advanced oral submucous fibrosis: our experience

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Severe oral submucous fibrosis (OSMF) poses problem with maintenance of oral hygiene,detection of malignancies and maintenance of nutrition. Surgical treatment includes release of fibrous bands with or without reconstruction for the raw area and postoperative physiotherapy.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; All cases with OSMF who underwent surgical management at our institute were included in our study. The demographic data, preoperative interincisor distance, local examination was recorded. All patients underwent contrast enhanced computed tomography scan of head and neck to rule out hidden malignancy. All cases underwent OSMF band release with or without reconstruction. All patients were instructed for vigorous mouth opening exercise. All patients were followed upto 6 months and further divided into two groups depending upon whether they followed physiotherapy advice or not.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; 13 patients of age group 18-47 years were included in our study. Male to female ratio was 1.6:1. Pre-operative mean interincisor distance was 7.5 mm whereas post-operative it was 19.5 mm. Patients who had followed mouth opening exercise were having a mean increase of 15 mm more as compared to those who did not.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Even after surgical management of severe OSMF, mouth opening exercise remains the key factor for maintenance of mouth opening.&lt;/p&gt;

Histochemical and Immunohistochemical Analysis of Collagen Fibers and Microvascular Density in Various Grades of Oral Submucous Fibrosis.

Background and Objective:This study was aimed to evaluate the collagen fibers qualitatively and its correlation with microvascular density in various grades of oral submucous fibrosis (OSMF). Material and Methods:The present study comprised of total 40 cases of oral submucous fibrosis. Picrosirius red staining was done on all the specimens’ sections. They were analyzed for the colour and orientation of collagen fibers. Morphometric measurements were done using image analysis on immunohistochemical stained sections for Factor VIII-related antigen and analyzed for microvascular density.Results:Picrosirius red polarizing microscopy results revealed that there was a shift in the colour of collagen fibers from greenish yellow to orange red and red colour as the severity of the oral submucous fibrosis increased. The collagen fibers showed mixed orientation in early oral submucous fibrosis and parallel orientation in advanced oral submucous fibrosis. There was a significant decrease in microvascular density from early to advanced oral submucous fibrosis.Conclusion:The change in the colours and orientation of collagen fibers in early and advanced oral submucous fibrosis could be attributed to the fibre thickness, type of collagen, alignment and packing, cross-linking of the fibers and the section thickness. However, in advanced cases the vascularity is reduced which may predispose to epithelial atrophy and subsequent malignant changes.

Interleukin 13 (IL-13) acts as a profibrotic cytokine for recruitment of myofibroblasts in oral submucous fibrosis

Oral submucous fibrosis (OSF) is a chronic inflammatory condition due to areca nut (Areca catechu) chewing which induces fibrosis leading to the difficulty in mouth opening. Various profibrotic cytokines and chemokines have been found involved in fibrosis. The present study was aimed to find the role of interleukin 13 (IL-13) in recruiting the myofibroblasts and as a causative factor for fibrosis in OSF. Twenty-five sections of OSF tissue and ten sections of normal mucosa were stained with IL-13, TGF-α1 and β-SMA antibodies using immunohistochemical method. Immunostaining was done to assess staining intensity and percentage of positive cells. The results were analyzed by SPSS software. The expression of all three markers IL-13, TGF- β1 and α-SMA showed significant difference between control and OSF (p < 0.001), control and early OSF (p < 0.001) control and advanced OSF (p < 0.001). No statistical difference was found between early OSF and advanced OSF. Significant expression of IL-13 and its correlation with TGF-β and α-SMA suggests its role in pathogenesis of OSF.

Role of angiogenesis in oral submucous fibrosis using vascular endothelial growth factor and CD34: An immunohistochemical study.

Oral submucous fibrosis (OSF) is an insidious, chronic, disabling disease, in which there is lack of perfusion due to reduced level of the vasculature and this is said to be responsible for the epithelial atrophy seen in OSF. The degree of vasculature of the affected mucosa and its effects on the epithelial thickness remains controversial till date. This study attempts to analyze the role of angiogenesis in OSF and its progression using vascular endothelial growth factor (VEGF) and CD34 markers. The study samples for the present study comprised of 10 cases each of early OSF, moderately advanced, advanced OSF, and 10 cases of normal oral mucosa were used as controls. All the cases were subjected to immunohistochemical staining with VEGF and CD34 markers. Among the different grades of OSF, we did not find any noticeable difference in VEGF expression although we found a upregulation in microvessel density (CD34) in early and moderately advanced OSF followed by a downregulation in advanced OSF. As the disease progresses, there is an increased production of the extracellular matrix component (collagen I and II and fibronectin) and results in fibrosis. Subsequently, it leads to the reduction in the level of corium vascularity and results in hypoxia which ultimately causes reduction and constriction of the vascular channels. This sequence of events alerts us to the relevance of early disease diagnosis and management in an irreversible pathology such as OSF.

Expression of cyclooxygenase 2 in oral submucous fibrosis: An immunohistochemical pilot study.

Introduction:Oral submucous fibrosis (OSF) is associated with inflammatory changes in at least some stages of the disease. Prostaglandin is one of the main inflammatory mediators and its production is controlled by various enzymes such as cyclooxygenase (COX). The genetic and pharmacological data strongly indicate that COX-2 should be investigated as a potential target for the prevention and treatment of OSF.Methodology:The study group comprised histologically confirmed specimens (n = 10 each) of early OSF, moderate OSF, advanced OSF and normal oral mucosa for comparison. Immunohistochemistry was performed with avidin–biotin technique and evaluated with scoring methods.Results:The difference in percentage of expression in normal tissue and OSF was statistically highly significant (P < 0.001). Positive COX-2 exhibited cytoplasmic staining. One-way analysis of variances test was performed to evaluate COX-2 expression in different grades of OSF. Cytoplasmic staining assessed in terms of intensity, percentage of expression and Q Score did not show any statistical difference (percentage of expression F = 0.029, P = 0.971; Q Score F = 0.154, P = 0.858).Conclusions:Our study indicates that COX-2 may be an important marker of disease progression and might be a reliable prognostic indicator.

Assessment and correlation between functional and histological staging of oral submucous fibrosis: A clinicohistopathologic study.

Background and Objective:Oral submucous fibrosis (OSMF) is a precancerous condition. It is widespread in the Asian subcontinent, with India bearing most of the burden. It is characterized by mucosal rigidity of varying intensity due to the fibroelastic changes of the juxta epithelial layer, resulting in a progressive inability to open the mouth. Early recognition with accurate staging of the disease and appropriate treatment planning is of utmost importance to prevent the malignant transformation and to improve the quality of life of the patient. In the present study, an attempt is made to clinically evaluate the condition and correlate it with the histopathological findings according to standard criteria.Materials and Methods:A hospital-based study was conducted on sixty OSMF patients. Detailed history was recorded, and functional staging was given depending on mouth opening. Punch biopsy was performed, and histological stages were given based on standard criteria. The data so received were mathematically evaluated to determine whether any correlation exists between the stages using Chi-square test.Results:The sixty patients were in the age range of 16–50 years. Male-to-female ratio was that of 97:3. The statistical analysis using Chi-square test showed statistically significant association (P < 0.001) between the functional and histologic stages.Conclusion:There is a definite correlation between functional and histological stages of OSMF which suggests that clinically advanced OSMF has extensive fibrosis histologically.

Risk analysis of malignant potential of oral verrucous hyperplasia: A follow-up study of 269 patients and copy number variation analysis.

Oral verrucous hyperplasia is commonly observed in the oral cavity of betel quid chewers and is a potential malignant disorder. However, the prognostic factors and genetic alterations of oral verrucous hyperplasia are unclear. We calculate the survival rate and prognostic factors using a Kaplan-Meier analysis and Cox proportional hazards regression model. Copy number variations were analyzed using a single-nucleotide polymorphism (SNP) array. The 5-year disease-free and cancer-free survival rates of patients with oral verrucous hyperplasia were approximately 40% and 70%, respectively. Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions were risk factors for malignant transformation, whereas dysplasia did not affect outcomes. The gene amplification of CTTN, FOLR3, ORAOV1, PPFIA1, and RNF121 were associated with the poor prognosis of oral verrucous hyperplasia. Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions are high-risk factors of patients with oral verrucous hyperplasia. The 5-copy number variation-associated genes could be used for early diagnosis and predicting the prognosis.

Comparison of microvessel density using CD34 and CD105 in oral submucous fibrosis and its correlation with clinicopathological features: An immunohistochemical study.

To compare immunohistochemical expression of CD34 and CD105 in oral submucous fibrosis (OSF) and normal oral mucosa (NOM) and correlate with clinicopathological features of OSF. Total of thirty clinically diagnosed and histologically confirmed cases of OSF and 15 NOM were included in the study. Tissues sections were immunostained using CD34 and CD105 antibodies. Twenty-eight cases (93.33%) were positive for CD34, and only 12 cases (40%) were positive for CD105 in OSF. In NOM all cases were positive for CD34 and only one case was positive for CD105. CD34 and CD105 significantly expressed in moderately advanced OSF when compared to very early, early, and advanced cases. It was found that the microvessel density (MVD) in NOM was significantly higher as compared to OSF and MVD decreased with advanced OSF. MVD was higher in CD34 when compared to CD105. MVD decreased with disease progression in OSF using both the markers. The role of CD34 in determining the premalignant nature of OSF could not be ascertained, since all endothelial cells were positive for CD34, whereas CD105 appeared to be more specific as it is associated with hypoxia-induced angiogenesis which is occurring in OSF due to hyalinization suggesting, CD105 to be more specific marker to determine neoangiogenesis in OSF. Thus further follow-up study of the cases positive for CD105 is required to determine the true nature of angiogenesis in OSF patients.

Oral submucous fibrosis: A clinico-histopathological correlational study.

The aim of this study was to correlate the clinical staging (clinical severity) with the histopathological staging (histopathological changes) of oral submucous fibrosis (OSF) patients, which would further assist the clinicians to formulate a definite treatment plan. The study group consisted of 50 subjects who were clinically and histologically diagnosed as OSF. Detailed information was gathered in a pretested proforma with emphasis on the various addictions. The clinical findings were noted; punch biopsy was performed followed by histological examination. Clinical and histological staging were divided into four stages, as Stages I-IV according to Khanna and Andrade classification. The 50 subjects were in the age range of 18-70 years, of which 20 patients were in clinical Group III, 15 were in histopathological stage III, 2, 1, and 2 in Stage II, Stage I, and Stage IV, respectively, out of 5 patients in clinical Group IV, 4 were in histopathological staging IV and 1 was in Stage III, out of 5 patients in clinical Group I, 3 and 2 were in histologic Stages II and I, respectively. Statistical analysis with Chi-square test showed high significance with P < 0.001. The correlation of clinical and histopathological staging was found to be highly significant, thus suggesting that the subject with clinically advanced OSF had extensive fibrosis histologically.