Differential Expression of Immunohistochemical Markers in Ameloblastoma & Ameloblastic Carcinoma: A Systematic Review and Meta-analysis of observational studies.

Background: Differentiating between ameloblastoma (AB) and ameloblastic carcinoma (AC) is difficult, especially when AB has atypical cytological characteristics or an uncommon clinical history. This systematic review and meta-analysis aimed to elucidate the differential expression of immunohistochemical markers between AB and AC. Methods: We conducted a thorough search of PUBMED and SCOPUS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify cross-sectional studies that compared the expression of immunohistochemical markers in AB and AC. We used a random-effects model to analyze the risk ratios and their corresponding 95% confidence intervals (CIs). The quality of the included studies was assessed using the Newcastle-Ottawa scale. The Egger's test was used to assess publication bias. Results: In total, 301 articles were identified. After excluding irrelevant titles and abstracts, 86 articles were selected for full-text review. We categorized the 41 markers into proliferative and non-proliferative markers. Among non-proliferative markers, nuclear markers were differentially expressed in AB and AC. SOX2 was the only marker that significantly differentiated AB and AC, with an RR of -0.19 (CI 0.10-0.36, I2=0). Conclusion: The current evidence suggests the significance of SOX2 in differentiating between AB and AC, warranting prospective confirmation in well-defined extensive studies. We highlight the paucity of high-quality replicated studies of other markers in this field. Collaborative efforts with standardized techniques are necessary to generate clinically useful immunohistochemical markers.

Analyzing working time and efficient caries removal using a novel bioactive caries detecting dye and air polisher prophy for caries excavation: randomised clinical trial.

OBJECTIVES: This study aims to analyze the working time consumed during caries excavation and pain perception while using a novel Bioactive caries-detecting dye solution (BCD), an Air Polisher Prophy and a combination. MATERIALS AND METHODS: Four groups (in each group, n = 20 permanent teeth) were selected from 60 people between 17 and 40 years of age. The study included teeth with occlusal dentinal caries in the molars with cavity entrance sizes of less than 2 mm (clinically and radiographically). Randomization software was used to assign patients to various groups. Group A: Conventional Rotary Drilling, Group B: BCD + Mechanical Excavation (Spoon Excavator), Group C: Air Polisher Prophy, and Group D: BCD + Air Polisher Prophy 0.5 mL BCD was applied with a micro brush to the carious tooth surface for 40 s in groups B and D. After that, radiographs were performed to see if the radiopaque extension was visible. For mechanical caries extraction, a spoon excavator was used for group B, and an air polisher prophy was employed for group D. For mechanical caries extraction, a spoon excavator was utilized for group B. An air polisher prophy was employed for group D. Multiple applications of the BCD were used in the event of residual caries. Working time and pain experienced during caries excavation were registered using the Verbal Pain Scale (VPS) (score 0-4), and caries removal was clinically graded using the modified Scale (score 0-5). RESULTS: The time taken was Group A, Group D, Group B, and Group C, according to statistical analysis using ANOVA and the Post Hoc Test (275.02, 403.8, 461.98, 615.41 s, respectively). Group A had the highest mean VPS (1.85), whereas Group B had the most minor pain (0.6), followed by Group D (1.2) and Group C (0.6). (1.45). Group C (2.35), followed by groups D (1.75), B (1.30), and A (1.30), had ineffective caries eradication (0.90). (p < 0.05). CONCLUSIONS: compared to group C, groups B and D took less time and had less/no pain while excavating caries. Compared to traditional mechanized caries removal methods, the chemo-chemical BCD can diagnose and aid in successful caries removal with minimal pain. CLINICAL RELEVANCE: The outcomes of the present study demonstrated that the chemo-chemical bioactive caries detecting dye solution has the potential to identify and help in effective caries removal before mechanized caries removal methods.

Comparison of Immunohistochemical Markers in Oral Submucous Fibrosis and Oral Submucous Fibrosis Transformed to Oral Squamous Cell Carcinoma-A Systematic Review and Meta-Analysis.

The objective of the study was to compare the expression of immunohistochemical (IHC) markers of oral submucous fibrosis (OSMF) (non-transformed group) to those of oral squamous cell carcinoma (OSCC) transformed from OSMF (transformed group). The search for comparative cross-sectional studies was carried out in PubMed and Scopus abiding to the PICO criteria, where expression of IHC markers in OSMF were compared with that of OSCC transformed from OSMF. The cellular distribution, number of positive cases, staining intensity, and mean immunoreactive score (IRS) of each IHC marker were evaluated in both groups. A total of 14 studies were included in the systematic review, in which immunoexpression of 15 epithelial and 4 connective tissue biomarkers were evaluated. Expression of ß1-integrin, OCT-3, CD1a, CD207, survivin, Dickkopf-1, COX-2, hTERT, CTGF, MDM2, Ki-67, and α-SMA were increased during transformation of OSMF to OSCC. Conversely, expression of PTEN and lysyl oxidase decreased during transformation of OSMF to OSCC. Expression of a group of epithelial markers, such as COX2, hTERT, CTGF, survivin, MDM2, and p53, was 38 times lower in the non-transformed group cases compared to transformed group cases (95% CI: 58% to 10%; p = 0.01; and I2 = 90%). Meta-analysis of all markers involved in cell metabolism/apoptosis, which included ß1-integrin along with the above markers also suggested 42 times lower expression in the non-transformed group as compared to the transformed group (95% CI: 58% to 10%; p = 0.01; and I2 = 90%). Sub-group analyses on cytoplasmic and nuclear epithelial markers were inconclusive. Meta-analysis of connective tissue markers was also inconclusive. No publication bias was found. Instead of delving into numerous markers without a strong basis for their use, it is advisable to further study the markers identified in this study to explore their clinical utility.

Can Immunoexpression of Cancer Stem Cell Markers Prognosticate Tongue Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis.

The objective was to evaluate the association of the immunoexpression of cancer stem cell (CSC) markers with clinicopathological and survival outcomes in tongue squamous cell carcinoma (TSCC) patients. This systematic review and meta-analysis [PROSPERO (CRD42021226791)] included observational studies that compared the association of clinicopathological and survival outcomes with CSC immunoexpression in TSCC patients. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were used as outcome measures. Six studies identified the association with three surface markers (c-MET, STAT3, CD44) and four transcription markers (NANOG, OCT4, BMI, SOX2). The odds of early-stage presentation were 41% (OR = 0.59, 95% CI 0.42-0.83) and 75% (OR = 0.25; 95% CI 0.14-0.45) lower in CSC and SOX2 immuno-positive cases than immuno-negative cases, respectively. The odds of well-differentiated tumors in transcription marker immuno-positive cases were 45% lower compared to immuno-negative cases (OR = 0.55, 95% CI 0.32-0.96). The odds of positive lymph nodes were 2.01 times higher in CSC immuno-positive cases compared to immuno-negative cases (OR = 2.01, 95% CI 1.11-3.65). Mortality in immuno-positive cases was 121% higher than that in immuno-negative cases (HR = 2.21; 95% CI 1.16-4.21). Advanced tumor staging and grading, lymph node metastasis, and mortality were significantly associated with positive immunoexpression of CSC markers.

Spindle Cell Hemangioma of Lower Lip: The Fourth Case Report with Review of Literature.

Background: Spindle cell hemangioma previously known as spindle cell hemangioendothelioma is a benign vascular tumour with rare presentation in head and neck. Presentation in lip is even rarer with three cases reported previously. Method: This report describes a case of spindle cell hemangioma presented as an asymptomatic growth on lower lip of a 32-year-old male. Clinicopathological characterization of this case along with previously reported 15 cases of spindle cell hemangioma of head and neck were conducted. Result: Microscopic evaluation shows a well-circumscribed vascular neoplasm of spindled and epithelioid endothelial cells. Large ectatic thin-walled vascular spaces were seen engorged with RBCs. The neoplasm was CD31 positive. Slight predilection for female gender and young age were observed. Minimal possibility of recurrence was also observed. Conclusion: Spindle cell hemangioma needs to be considered in the differential diagnosis of vascular tumours of head and neck to avoid misdiagnosis of aggressive vascular neoplasms.

Perspective of nuclear fractal dimension in diagnosis and prognosis of oral squamous cell carcinoma.

Background: Owing to the restricted predictive value of conventional prognostic factors and the inconsistent treatment strategies, several oral squamous cell carcinoma (OSCC) patients are still over-treated or under-treated. In recent years, computer-assisted nuclear fractal dimension (nFD) has emerged as an objective approach to predict the outcome of OSCC. Objective: This study is an attempt to find out the differences in nFD values of epithelial cells of normal tissue, fibroepithelial hyperplasia, verrucous carcinoma, and OSCC. Further effort to evaluate the predictive potential of nFD of tumor cells for cervical lymph node metastasis (cLNM) was also assessed. Methodology: Formalin-fixed paraffin-embedded blocks of OSCC tissues of patients treated with neck dissection were collected. Photomicrographs of H-&E-stained sections were subjected to the image analysis by ImageJ and Python programming to calculate nFD. The association of categorical variables with nFD was studied using cross-tabulation procedure and the Fisher exact test. Receiver operating curve analysis was performed to find out cutoff value of nFD. A logistic regression model was developed to test the individual and combined predictive potential of grading and nFD for cLNM. Results: A significant difference between the mean nFD of healthy cells and malignant epithelial cells was observed (P = 0.01). nFD was not found to be an independent predictor of cLNM, although nFD and grading together demonstrated significant predictive potential (P = 0.004). Conclusion: nFD combined with grading can predict lymph node metastasis in OSCC. To the best of our knowledge, this is the first study of its kind.

Are Survival Outcomes Different for Young and Old Patients with Oral and Oropharyngeal Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to address whether age can be a determinant of overall survival (OS), disease-free survival (DFS), recurrence, distant metastasis (DM) and second primary (SP) in surgically treated oral and oropharyngeal squamous cell carcinoma (OOPSCC). A total of 4981 cases and 44254 controls from 25 comparative observational studies were included in the analysis. A significantly better OS (matched subgroup analysis: OR 1.64; 95% CI 1.31-2.04, overall analysis: OR 1.48; 95% CI 1.09-2.01) was observed in young patients compared to older adults, with heterogeneity ranging from moderate to severe. Worse DFS (unmatched subgroup analysis OR 0.43; 95% CI 0.27-0.68) was observed in young patients compared to older adults with minimal to moderate heterogeneity. The frequency of recurrence (OR 1.49; 95% CI 1.10-2.02) and DM (OR 1.83; 95% CI 1.10-3.03) was significantly higher in the young patients, as found in unmatched and matched subgroup analysis, with the least heterogeneities. Young age can be considered as an independent prognostic factor for recurrence and distant metastases in OOP-SCC. Larger and methodologically robust observational studies with longer follow-up are needed to establish the definitive role of age as an independent prognostic factor on OS and DFS in OOPSCC.

Amelanotic melanoma of the palate: report of a case.

Primary amelanotic melanoma is an infrequent occurrence in the oral cavity. Owing to the high rate of local invasion and distant metastasis, oral amelanotic melanoma (OAM) carries a very poor prognosis. The absence of pathognomonic clinical and routine histological features in OAM is the reason for diagnosticdelay, which further worsens the prognosis. This case report discusses the masquerading nature of OAM that was clinically and histologically mimicking several malignant neoplasms. This case also demonstrates the poor prognosis of OAM. The objective of presenting this case is that the diagnostic delay of OAM can be avoided through enhanced clinical awareness and subsequent appropriate immunohistochemical investigations, in addition to the routine H&E-stained histopathological evaluation.

Innocuous presentation of ameloblastic carcinoma.

Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits diverse clinical and radiological presentations. In fact there are several differential diagnoses during histopathological evaluation too. Lack of adequate reports could not establish the predominant demographic, clinical and radiological presentations. For the same reasons, the role of adjuvant radiotherapy and chemotherapy is also unsubstantiated yet. This case discusses the innocuous clinical and radiological presentation of ameloblastic carcinoma in a 55-year-old man where the diagnostic confirmation was achieved through histopathological evaluation. The differential diagnoses, treatment and follow-up details of this case are discussed in light of the previous published case reports and systematic reviews of case reports in an attempt to increase the sensitisation among dentists towards ameloblastic carcinoma.

A Plausible Proposition of CCL20-Related Mechanism in Fusobacterium nucleatum-Associated Oral Carcinogenesis.

OBJECTIVE: The objective of this prospective observational case-control study is to evaluate the prevalence of Fusobacterium nucleatum in the tissues of oral squamous cell carcinoma (OSCC). Reconnoitering the CCL20-related mechanism of carcinogenesis in Fusobacterium nucleatum-positive OSCC is another objective. METHODOLOGY: Tissues from 50 OSCC patients and 30 healthy oral tissues were collected. The prevalence of Fusobacterium nucleatum was evaluated in both tumour and healthy tissue by polymerase chain reaction. The immunohistochemistry of OSCC tissues was conducted to evaluate the difference in the expression of CCL20 between Fusobacterium nucleatum-positive and -negative OSCC tissues. RESULTS: Fusobacterium nucleatum was significantly (p < 0.001) prevalent in OSCC tissues (74%), compared to healthy tissues (26%). No association of Fusobacterium nucleatum or CCL20 immuno-expression with any clinical or histopathological features of OSCC was observed. While the intensity of CCL20 immuno-expression did not differ (p = 0.053), the CCL20-positive cell population was significantly different (p = 0.034) between Fusobacterium nucleatum-positive and -negative OSCC. CONCLUSION: Fusobacterium nucleatum is possibly prevalent in oral cancer tissues in the Indian population. By using immunohistochemistry, this is the first study to propose that the carcinogenesis in Fusobacterium nucleatum-positive OSCC may be CCL20-related. The findings enrich the knowledge of mechanisms involved in Fusobacterium nucleatum-mediated oral carcinogenesis.

Giant ossifying fibroma of the maxilla: an unusually aggressive presentation in a 21-year-old woman.

We present a rare case of a huge aggressive ossifying fibroma of the maxilla in a 21-year-old female patient with involvement of the maxillary antrum, nasal cavity, orbit and the ethmoid sinus with a unique radiologic appearance for documentation.

Whole-Exome Sequencing Analysis of Oral Squamous Cell Carcinoma Delineated by Tobacco Usage Habits.

Oral squamous cell carcinoma (OSCC) is a common cancer of the oral cavity in India. Cigarette smoking and chewing tobacco are known risk factors associated with OSCC. However, genomic alterations in OSCC with varied tobacco consumption history are not well-characterized. In this study, we carried out whole-exome sequencing to characterize the mutational landscape of OSCC tumors from subjects with different tobacco consumption habits. We identified several frequently mutated genes, including TP53, NOTCH1, CASP8, RYR2, LRP2, CDKN2A, and ATM. TP53 and HRAS exhibited mutually exclusive mutation patterns. We identified recurrent amplifications in the 1q31, 7q35, 14q11, 22q11, and 22q13 regions and observed amplification of EGFR in 25% of samples with tobacco consumption history. We observed genomic alterations in several genes associated with PTK6 signaling. We observed alterations in clinically actionable targets including ERBB4, HRAS, EGFR, NOTCH1, NOTCH4, and NOTCH3. We observed enrichment of signature 29 in 40% of OSCC samples from tobacco chewers. Signature 15 associated with defective DNA mismatch repair was enriched in 80% of OSCC samples. NOTCH1 was mutated in 36% of samples and harbored truncating as well as missense variants. We observed copy number alterations in 67% of OSCC samples. Several genes associated with non-receptor tyrosine kinase signaling were affected in OSCC. These molecules can serve as potential candidates for therapeutic targeting in OSCC.

Proteomic Alterations Associated with Oral Cancer Patients with Tobacco Using Habits.

Tobacco abuse is a major risk factor associated with the development of oral squamous cell carcinoma. Differences in molecular aberrations induced by tobacco exposure by chewing or smoking form are not well studied in case of oral cancer. We used tandem mass tag-based quantitative proteomic approach to delineate proteomic alterations in oral cancer patients based on their history of tobacco using habits (patients who chewed tobacco, patients who smoked tobacco, and those with no history of tobacco consumption). Our data identified distinct dysregulation of biological processes and pathways in each patient cohort. Bioinformatics analysis of dysregulated proteins identified in our proteomic study revealed dysregulation of collagen formation and antigen processing/presentation pathway in oral cancer patients who smoked tobacco, whereas proteins associated with the process of keratinization showed enrichment in patients who chewed tobacco. In addition, we identified overexpression of proteins involved in immune pathways and downregulation of muscle contraction-mediated signaling events in all three cohorts, irrespective of tobacco using habits. This study lays the groundwork for identification of protein markers that may aid in identification of high-risk patients for cancer development based on the history of tobacco exposure habits.

An integrated approach for identification of a panel of candidate genes arbitrated for invasion and metastasis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is known for its aggressiveness associated with poor prognosis. The molecular mechanisms underlying the invasion and metastasis are still poorly understood. An improved understanding of these mechanisms shall precede the development of new diagnostic tools and targeted therapies. We report an integrated approach using bioinformatics to predict candidate genes, coupled with proteomics and immunohistochemistry for validating their presence and involvement in OSCC pathways heralding invasion and metastasis. Four genes POSTN, TNC, CAV1 and FSCN1 were identified. A protein-protein interaction network analysis teamed with pathway analysis led us to propose the role of the identified genes in invasion and metastasis in OSCC. Further analyses of archived FFPE blocks of various grades of oral cancer was carried out using TMT-based mass spectrometry and immunohistochemistry. Results of this study expressed a strong communiqué and interrelationship between these candidate genes. This study emphasizes the significance of a molecular biomarker panel as a diagnostic tool and its correlation with the invasion and metastatic pathway of OSCC. An insight into the probable association of CAF's and these biomarkers in the evolution and malignant transformation of OSCC further magnifies the molecular-biological spectrum of OSCC tumour microenvironment.