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.

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 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.