Evaluation of plasma fibrinogen degradation products, D-dimer, and mast cells in oral submucous fibrosis.

Background: Oral submucous fibrosis (OSF), a premalignant condition, demands early diagnosis and treatment for an improved prognosis of the patients. Being a chronic inflammatory disease, various markers of inflammation can be used to predict the prognosis of the disease. The present study was undertaken to assess the plasma levels of fibrinogen degradation products (FDPs), D-dimer, and mast cell density (MCD) in patients with OSF. Materials and Methods: Forty histopathologically confirmed cases of OSF and 10 age- and sex-matched individuals were included in the study. Two ml of venous blood was obtained from all the study participants and was evaluated for the levels of FDPs, d-dimer, and mast cell densities. Results: Comparison of mean plasma levels of FDPs and D-dimer showed a statistically significant increase with the increase in the grades of OSF. Also, a significant association was evident between the plasma FDPs and D-dimer levels. The values of mean mast cell densities from grade I to grade IV OSF were 191.1/mm2, 258.5/mm2, 182.4/mm2, and 165.7/mm2, respectively, and were significantly higher than the value in NOM i.e., 86.5/mm2. There was a statistically significant increase in the values of mast cell densities from grade I to grade II OSF, with grade II OSF showing the highest mast cell densities among all the grades, and the values decreased toward grades III and IV OSF, with grade IV showing the least mast cell densities. Conclusion: Excessive areca nut chewing may stimulate collagen synthesis by fibroblasts, enhancing fibrosis, and in turn, raising the plasma fibrinogen levels and thereby the FDPs and d-dimers associated with the advancement of the grade of OSF.

Ki-67, CD105, and α-smooth muscle actin expression in oral squamous cell carcinoma corresponds with different forms of tobacco consumption habits.

Background: Association with variety of etiological agents is one of the characteristic features of oral squamous cell carcinoma (OSCC). We hypothesized the existence of tobacco consumption habit-based heterogeneity in the immunohistochemical expression of carcinogenesis relevant molecular markers in OSCC. Hence, the present study was conducted to investigate the carcinogenesis relevant three commonly expressed markers (Ki-67, CD105, and α-smooth muscle acting [SMA]) in various forms of tobacco consumption habits in OSCC patients. Materials and Methods: A total of 217 patients of OSCC were included in the study, and based on the habit, they were broadly categorized into tobacco lime (TL), TL and areca nut (TLAN), and areca nut (AN). Further, categorization was done on the basis of absence or presence of additional habit of smoking. Immunohistochemistry (IHC) was performed using Ki-67, CD105, and α-SMA markers on formalin-fixed paraffin-embedded tissues. Results: TLAN (62.21%) was the most common habit noted in OSCC patient followed by TL (20.73%) and AN (15.20%). The additional habit of smoking was observed in 31.11% and 25.92% of TL and TLAN habits of OSCC patients, respectively. All the three markers (Ki-67, CD105, and α-SMA) showed statistically significant differences in the habit group such as TL, TLAN, and AN (P < 0.001). Although the expression of all the three markers was increased in TL as compared with TLAN, differences were not statistically significant. When these markers were compared in with and without smoking category, only TLAN with smoking and TLAN without smoking showed statistically significant differences in the expression of all three markers. Conclusions: Ki-67 CD105 and α-SMA immunohistochemical expression in OSCC corresponds with different forms of tobacco consumption habits. Habit-related unique carcinogenesis events are reflected at IHC level thus providing proof of concept for future studies.

Molecular Signatures of Tumour and Its Microenvironment for Precise Quantitative Diagnosis of Oral Squamous Cell Carcinoma: An International Multi-Cohort Diagnostic Validation Study.

BACKGROUND: Heterogeneity in oral potentially malignant disorder (OPMD) poses a problem for accurate prognosis that impacts on treatment strategy and patient outcome. A holistic assessment based on gene expression signatures from both the tumour cells and their microenvironment is necessary to provide a more precise prognostic assessment than just tumour cell signatures alone. METHODS: We reformulated our previously established multigene qPCR test, quantitative Malignancy Index Diagnostic System (qMIDS) with new genes involved in matrix/stroma and immune modulation of the tumour microenvironment. An algorithm calculates and converts a panel of 16 gene mRNA expression levels into a qMIDS index to quantify risk of malignancy for each sample. RESULTS: The new qMIDSV2 assay was validated in a UK oral squamous cell carcinoma (OSCC) cohort (n = 282) of margin and tumour core samples demonstrating significantly better diagnostic performance (AUC = 0.945) compared to previous qMIDSV1 (AUC = 0.759). Performance of qMIDSV2 were independently validated in Chinese (n = 35; AUC = 0.928) and Indian (n = 95; AUC = 0.932) OSCC cohorts. Further, 5-year retrospective analysis on an Indian dysplastic lesion cohort (n = 30) showed that qMIDSV2 was able to significantly differentiate between lesions without transformation and those with malignant transformation. CONCLUSIONS: This study validated a novel multi-gene qPCR test on a total of 535 tissue specimens from UK, China and India, demonstrating a rapid minimally invasive method that has a potential application for dysplasia risk stratification. Further study is required to establish if qMIDSV2 could be used to improve OPMD patient management, guide treatment strategy and reduce oral cancer burden.

Ki67 Labelling Index predicts clinical outcome and survival in oral squamous cell carcinoma.

OBJECTIVE: To investigate the Ki 67 expression and its correlation with clinicopathological features and 3 years as well as 5 years survival rate in oral squamous cell carcinoma (OSCC). METHODOLOGY: Total 217cases of OSCC primarily treated with surgery with or without radiation were included. All patients were followed up for 3 years and 150 were followed up of 5 years for disease free survival. The immunohistochemistry was carried out on neutral buffered formalin fixed paraffin embedded tissue to evaluate the expression of Ki67. RESULTS: The Ki67 labeling index (LI) was significantly higher with respect to adverse clinicopathological parameters such as histopathological grading (p<0.001), clinical TNM staging (p<0.001) and nodal metastasis (p<0.001). The OSCC patients survived for less than 3 and 5 years were showed significantly higher Ki67 LI as compared to diseases free survived more than 3 and 5 years(p<0.001). The three years survival rate of OSCC patient significantly higher with low Ki67 LI (≤45) 96.2%, followed by moderate Ki67 LI (46 to 60) 60.7% and high Ki67 LI (≥61) 37.7% (p<0.001). The five years survival rate of OSCC patient statistically significantly higher with low Ki67 LI (≤45)93.3%, followed by moderate Ki67 LI (46 to 60) 46.8% and Ki67 LI (≥61) 23.3% (p<0.001). CONCLUSION: The measurement of cell proliferative activity by using Ki67 antigen expression in individual OSCC might provide unique, predictive information on clinical outcome, prognosis and deciding treatment modalities in OSCC.

Ki67 Labelling Index predicts clinical outcome and survival in oral squamous cell carcinoma

Abstract Objective To investigate the Ki 67 expression and its correlation with clinicopathological features and 3 years as well as 5 years survival rate in oral squamous cell carcinoma (OSCC). Methodology Total 217cases of OSCC primarily treated with surgery with or without radiation were included. All patients were followed up for 3 years and 150 were followed up of 5 years for disease free survival. The immunohistochemistry was carried out on neutral buffered formalin fixed paraffin embedded tissue to evaluate the expression of Ki67. Results The Ki67 labeling index (LI) was significantly higher with respect to adverse clinicopathological parameters such as histopathological grading (p<0.001), clinical TNM staging (p<0.001) and nodal metastasis (p<0.001). The OSCC patients survived for less than 3 and 5 years were showed significantly higher Ki67 LI as compared to diseases free survived more than 3 and 5 years(p<0.001). The three years survival rate of OSCC patient significantly higher with low Ki67 LI (≤45) 96.2%, followed by moderate Ki67 LI (46 to 60) 60.7% and high Ki67 LI (≥61) 37.7% (p<0.001). The five years survival rate of OSCC patient statistically significantly higher with low Ki67 LI (≤45)93.3%, followed by moderate Ki67 LI (46 to 60) 46.8% and Ki67 LI (≥61) 23.3% (p<0.001). Conclusion The measurement of cell proliferative activity by using Ki67 antigen expression in individual OSCC might provide unique, predictive information on clinical outcome, prognosis and deciding treatment modalities in OSCC.

Ki67, CD105, and α-SMA Expression Supports Biological Distinctness of Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

BACKGROUND: The clinicopathological distinctness of oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSF) is well known; however, the molecular distinctness of this unique OSCC-OSF has not been investigated to date. With this in mind, we compared the expression of Ki67, CD105, and α-SMA between OSCC-OSF and oral squamous cell carcinoma (OSCC). METHODS: Formalin-fixed paraffin-embedded tissues of 105 OSCC-OSF and 112 OSCC cases were subjected to immunohistochemistry for evaluation of Ki67, CD105, and α-SMA expression. RESULTS: Ki67 (labeling index) LI, MVD and α-SMA expression were significantly higher in OSCC compared to OSCC-OSF. Ki67 LI and MVD was significantly higher in OSCC compared to OSCC-OSF in parameters such as well-differentiated, early TNM stage, non-metastatic, and more than 3-year survival. α-SMA expression was significantly higher in OSCC compared to OSCC-OSF in parameters such as moderate differentiation, metastatic lesions, and survival less than 3 years. Ki67 LI, MVD and α-SMA showed significant positive correlation with each other in OSCC and OSCC-OSF. CONCLUSION: Proliferation, neoangiogenesis and myofibroblast differentiation were significantly higher in the OSCC group compared to the OSCC-OSF group. This suggests the biological distinctness of OSCC-OSF, which could help the future development of targeted therapies.

Ki67, CD105 and α-smooth muscle actin expression in disease progression model of oral submucous fibrosis.

AIM: The aim of this study was to investigate the expression of Ki67, CD105 and α-smooth muscle actin (α-SMA) expression in oral submucous fibrosis (OSF) and oral squamous cell carcinoma in the background of OSF (OSCC-SMF). METHODS: The study was carried out on paraffin-embedded tissues of 30 normal oral mucosa (NOM), 50 OSF cases and 105 OSCC-SMF. The immunohistochemistry was carried out to evaluate the expression of Ki67, CD105 and α-SMA antigen. RESULTS: Ki67 labelling index (LI), CD105 and α-SMA expression showed increasing trend from NOM, low-risk epithelial dysplasia (LRED), high-risk epithelial dysplasia (HRED), well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma to poorly differentiated squamous cell carcinoma. However, there was no significant difference of α-SMA expression between HRED and WDSCC. In OSCC-SMF, Ki67 LI, CD105 and α-SMA were significantly higher in advanced clinical TNM stage, metastasis and less than 3 years patient survival as compared with early clinical TNM stage, non-metastasis and 3 years or more patient survival. CONCLUSION: Ki67 LI, α-SMA and CD105 expression alone or together correspond with the disease progression model of SMF. Hence, expression of these markers can be used as a predictive marker of clinical outcome of OSCC-SMF.

Oral submucous fibrosis: An enigmatic morpho-insight.

Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disease affecting oral, oropharyngeal, and sometimes the esophageal mucosa. It is characterized by the progressive fibrosis of the submucosal tissue. The pathogenesis of OSMF has been directly related to the habit of chewing areca nut and its commercial preparation, which is widespread in Indian subcontinent and Southeast Asia. The areca nut has been classified as a "group one human carcinogen." Oral squamous cell carcinoma in the background of OSMF is one of the most common malignancies in South and Southeast Asian countries. Malignant transformation has been reported in 7%-12% cases of OSMF. Histopathological spectrum of OSMF includes the apparent alterations observed in the epithelium and connective tissue. Epithelial atrophy and sometimes epithelial hyperplasia with or without dysplasia are the peculiar alterations seen in the epithelium. In the connective tissue, there is extracellular matrix remodeling which results in excessive collagenization. Further cross-linking of collagen leads to hyalinization which makes the collagen resistant to proteolysis. Owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu, that is, hypoxia. This tissue hypoxia elicits angiogenesis which may result in the malignant transformation of OSMF. Perpetual irritation of areca nut and its constituents to the oral mucosa leads to upregulation of pro-inflammatory cytokines and further juxtaepithelial inflammation. Thus, these coordinated reactions in epithelium and connective tissue leads the OSMF toward malignant transformation.

Multidisciplinary approach to bilaterally missing lateral incisors: A case report.

Maxillary lateral incisors are most common teeth to be found missing. They also are the most common teeth that need esthetic replacement. A 23-year-old female patient with missing maxillary lateral incisors was treated orthodontically: laterals were replaced with implants. Challenges while doing this case are discussed in the following case report.

Ki67, CD105, and α-SMA expression supports the transformation relevant dysplastic features in the atrophic epithelium of oral submucous fibrosis.

BACKGROUND: The grading of oral epithelial dysplasia is not possible in the atrophic epithelium of oral submucous fibrosis (OSMF). Recently, we found that features such as increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, increased nuclear size, and hyperchromasia represent transformation-relevant dysplastic features in the atrophic epithelium of OSMF. The presence of these features can be considered a high-risk feature for patients. However, these findings have not been tested and authenticated using markers relevant to oral carcinogenesis. METHOD: Paraffin-embedded tissues from 30 normal oral mucosa (NOM) and 50 OSMF were retrieved from 2008 to 2016 and subjected to immunohistochemical expression using Ki67, CD105 and α-SMA antibodies. RESULTS: Ki67 LI showed significant increases from NOM (12.47±2.34) to LRED (23.47±3.75) to HRED (34.31±7.31) (<0.0001). Similarly, MVD was increased significantly from NOM (3.53±5.17) to LRED (27.57±12.25) to HRED (46.18±12.55) (p<0.0001). The expression of α-SMA was significantly increased from LRED (0.21±0.41) to HRED (1.13±0.56) (<0.0001). The Ki67 LI and α-SMA; MVD and α-SMA; and Ki67Ki67 LI and MVD in NOM, LRED and HRED showed a statistically significant positive correlation (P<0.0001). The increase in Ki67 LI was directly proportional to MVD and α-SMA expression from NOM to LRED to HRED (P<0.0001). The connective tissue stroma of NOM lacks α-SMA expression. Mild myofibroblast expression was noted in 4 cases of LRED (14.28%) and in 18 cases of HRED (81.81%). Moderate expression was noted only in 4 cases of HRED (22.22%). CONCLUSION: Ki67 LI, CD105, and α-SMA expression showed significant differences between normal, LRED and HRED. These findings further support that features such as increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, and hyperchromasia could be transformation-relevant dysplastic features.

In vivo autofluorescence of oral squamous cell carcinoma correlated to cell proliferation rate.

CONTEXT: Loss of cell differentiation and increased cellular proliferative activity during malignant transformation leads to alteration of biochemical content of cells. This is reflected in the fluorescence profile of tissues. AIMS: (1) To evaluate the efficacy of autofluorescence in clinical detection of oral cancer. (2) To correlate it with the rate of cell proliferation by analyzing argyrophilic nucleolar organizer regions (AgNORs). SUBJECTS AND METHODS: Autofluorescence status was studied by devising a visual enhancement system using ultraviolet light, followed by an incisional biopsy. Tissue was sent for fluorescence spectroscopy and analyzed by routine histopathology and AgNORs staining. The obtained results were statistically analyzed using Chi-square test (P < 0.05) and one-way analysis of variance. RESULTS: A statistically significant correlation was seen between autofluorescence (AF) and clinical diagnosis as well as autofluorescence and histopathological diagnosis. The importance of autofluorescence as a screening tool was further supported by a statistically significant correlation between autofluorescence status and cell proliferative rate. CONCLUSION: A preliminary effort was attempted at delving into this relatively unexplored arena of optical biopsy systems through this study. They can be used to monitor treatment and potential complications, surgical margins, detection of nodal metastasis, etc. They can provide a diagnosis noninvasively, in situ, and in real time.

Dysplastic features relevant to malignant transformation in atrophic epithelium of oral submucous fibrosis: A preliminary study.

BACKGROUND: The grading of oral epithelial dysplasia (OED) is not applicable to oral submucous fibrosis (OSMF) cases due to the presence of atrophic epithelium. The mucosal margins associated with resected OSCC specimens are often closely related to transformed cells. In this study, we compared the histomorphological alterations (dysplastic features) in the atrophic epithelium of OSMF patients with the mucosal margins of OSCC associated with OSMF (OSCC-OSMF). METHODS: We evaluated 17 dysplastic features in 37 patients with OSMF (biopsy site: buccal mucosa) and 37 patients with OSCC-OSMF (mucosal margins involving buccal mucosa) using histopathological staining. RESULTS: Dysplastic features, such as keratin pearls within rete ridges, nuclear pleomorphism, and atypical mitotic figures, were not observed in the epithelium of the OSMF or OSCC-OSMF groups. Basal cell hyperplasia (P = .016), abnormal superficial mitosis (P = .010), increased nuclear-cytoplasmic ratio (P = .034), and hyperchromasia (P = .031) were predominantly seen in the OSCC-OSMF group. We found no statistically significant differences in the following parameters: irregular epithelial stratification (P = 1.00), loss of basal cell polarity (P = .237), presence of drop-shaped rete ridges (P = .077), increased number of mitotic figures (P = .154), premature keratinization in single cells (P = .499), anisonucleosis (P = .289), anisocytosis (P = .079), cellular pleomorphism (P = .317), and increased number and size of nucleoli (P = .129). CONCLUSION: Increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, and hyperchromasia are high-risk features for OSMF, and affected patients should be followed on a priority basis for the early detection of OSCC.

Ki67, CD105, and α-SMA expressions better relate the binary oral epithelial dysplasia grading system of World Health Organization.

BACKGROUND: The binary system of oral epithelial dysplasia (OED) has never been investigated with reference to the carcinogenesis-related biomarkers. Hence, Ki67, CD105, and α-SMA immune-expressions were studied in oral potentially malignant disorders (OPMDs) to assess their relationship with the binary OED grading system of World Health Organization. METHODS: The study was carried out on paraffin-embedded tissues of 30 normal oral mucosa (NOM) and 140 OPMD cases. OPMD cases were classified into two groups "no/questionable/hyperkeratosis/mild"=low-risk epithelial dysplasia (LRED) and "moderate or severe"=high-risk epithelial dysplasia (HRED). The immunohistochemistry was carried out to evaluate the expression of Ki67, CD 105, and α-SMA antigen. RESULTS: According to the binary grading system of WHO, 69 (49.28%) cases were LRED, while 71 (50.71%) case showed HRED. There was significant increase in Ki67 labeling index (LI) from NOM to LRED to HRED (P=.000). Similarly, mean vascular density (MVD) also increased significantly from NOM to LRED to HRED (P=.000). The α-SMA expression was significantly higher in HERD compared to LRED and NOM (P=.000). A positive correlation was noted among Ki67 LI, MVD, and α-SMA expressions in NOM, LRED, and HRED (P=.000). CONCLUSION: The expressions of ki67, CD105, and α-SMA markers compliment binary grading system of OED in OPMDS, thus justifying its use in clinical practice.

Early Stage Oral Submucous Fibrosis is Characterized by Increased Vascularity as Opposed to Advanced Stages.

INTRODUCTION: The degree of vascularity of the diseased mucosa in Oral Submucous Fibrosis (OSMF) has always been a matter of debate with conflicting results. Knowledge of this aspect is important to understand pathogenesis of OSMF, which in future could be translated into therapeutic strategies. AIM: In the present study, attempt has been made to investigate parameters like Mean Vascular Density (MVD), Total Vascular Area (TVA) and Mean Vascular Area (MVA) using CD34 antibody. MATERIALS AND METHODS: Forty five previously untreated histopathologically diagnosed cases of OSMF were retrieved from archives and fifteen age and sex matched healthy volunteers without habits were included in the control group. Sections were immunohistochemically stained for CD 34 and morphometric analysis was performed. For statistical analysis ANOVA, Kruskal Wallis test and Mann Whitney U tests were used and p-values <0.05 were considered statistically significant. RESULTS: MVD was more in Stage I OSMF followed by Control, Stage II and Stage III with statistically significant differences (p< 0.001). Statistically significant differences were observed in the MVD between control versus Stage III OSMF. Similarly, TVA was statistically significant when compared between control versus OSMF, control versus Stage II OSMF, control versus Stage III OSMF, Stage I versus Stage II OSMF, Stage I versus Stage III OSMF, and Stage II versus Stage III OSMF. For MVA, significant differences were between control versus OSMF, control versus Stage II OSMF, control versus Stage III OSMF, Stage I versus Stage III OSMF and Stage II versus Stage III OSMF. CONCLUSION: Angiogenesis is seen in early stages of OSMF with decreasing trend in advanced stages. Decreased vascular areas seen in advanced stages could be attributed to the increasing fibrosis surrounding the blood vessels.

Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinicopathological entity with better prognosis.

BACKGROUND: The aim of this study was to compare the clinicopathological features of oral squamous cell carcinoma in the background of oral submucous fibrosis (OSCC-OSMF) and oral squamous cell carcinoma (OSCC). METHODS: A total of 217 cases of OSCC were retrieved from achieves for the analysis. OSCC-OSMF cases were segregated on the basis of history and clinicopathological parameters. RESULTS: The study included 217 patients of which 112 had OSCC and 105 OSCC-OSMF. OSCC-OSMFs were younger compared with OSCC. Overall oral cancer was noted predominantly in males compared to females. The number of OSCC-OSMF was more in clinical TNM stage I and stage II as compared to OSCC, whereas the number of OSCC was more in stage III and stage IV compared to OSCC-OSMF. Histological presentation of well-differentiated squamous cell carcinoma was significantly more in OSCC-OSMF compared to OSCC, whereas moderately differentiated squamous cell carcinoma was significantly more in OSCC compared to OSCC-OSMF. Regional lymph node metastasis was significantly higher in OSCC compared to OSCC-OSMF. Three-year disease-free survival rate was significantly higher in OSCC-OSMF compared to OSCC. CONCLUSION: The OSCC-OSMF was found to be a clinicopathologically distinct entity with a better grade of tumor differentiation, less incidence of nodal metastases, and early detection (early clinical TNM stage) compared to OSCC. All these factors probably contribute to a better prognosis and increased 3-year disease-free survival in OSCC-OSMF patients.

Oxidative and antioxidative mechanisms in oral cancer and precancer: a review.

Development of cancer in humans is a multistep process. Complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli and important amongst this is generation of reactive oxygen species (ROS). Reactive radicals and non-radicals are collectively known as ROS. These can produce oxidative damage to the tissues and hence are known as oxidants in biological system. Many researchers have documented the role of ROS in both initiation and promotion of multistep carcinogenesis. To mitigate the harmful effects of free radicals, all aerobic cells are endowed with extensive antioxidant defence mechanisms. Lowered antioxidant capacity or the oxidant-antioxidant imbalance can lead to oxidative damage to cellular macromolecules leading to cancer. Oral cavity cancer is an important cancer globally and tobacco is the primary etiological factor in its development. Tobacco consumption exposes the oral epithelium to toxic oxygen and nitrogen free radicals that can affect host antioxidant defence mechanisms. Elevated levels of ROS and Reactive Nitrogen Species (RNS) and lowered antioxidants are found in oral precancer and cancer. Protection can be provided by various antioxidants against deleterious action of these free radicals. Treatment with antioxidants has the potential to prevent, inhibit and reverse the multiple steps involved in oral carcinogenesis. This review is an attempt to understand the interesting correlation between ROS and RNS mediated cell damage and enzymatic and non-enzymatic defence mechanisms involved in oral cancer development and its progression and the use of antioxidants in oral cancer prevention and treatment.

Tumor angiogenesis in keratocystic odontogenic tumor assessed by using CD-105 antigen.

BACKGROUND: The purpose of this study was to assess and compare angiogenesis with proliferative activity in Keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC) by using monoclonal mouse anti-human antibody against CD105 (endoglin). MATERIAL AND METHODS: Angiogenesis was assessed in 38 KCOT, 27 DCs and 19 Normal Oral Mucosa (NOM) by measuring the Mean Vascular Density (MVD), Total Vascular Area (TVA) and Mean Vascular Area (MVA). Cell proliferation was assessed by obtaining Ki-67 Labeling Index (Ki-67LI) in all the groups. RESULTS: Statistically significant difference was observed in MVD, TVA, MVA and Ki-67 LI between the KCOT, DC and NOM (P=0.000). The MVD, TVA, MVA and Ki-67 LI were significantly higher in KCOT than in DC and NOM (P=0.000). The Ki-67 LI was significantly higher in NOM than in DC (P=0.000). MVD (P=0.032) and TVA (P=0.038) were significantly higher in NOM than in DC. There was significant positive correlation between Ki-67 LI and MVD, Ki-67 and TVA and Ki-67 and MVA. CONCLUSION: The result suggests that CD105 (endoglin) is strongly expressed in microvessels of KCOT compared with that in Dentigerous cyst and Normal oral mucosa. Thus, it suggests that angiogenesis may be associated with locally aggressive biological behavior of KCOT. These findings further stress on the hypothesis that the stroma of KCOT could be regarded not just as a structural support of the cyst wall, but as playing a part in the neoplastic behavior of cyst.