Radicular variant of dens in dente (RDinD) in a patient undergoing radioisotope therapy.

Dense in dente is a developmental anomaly frequently encountered in permanent maxillary incisors, with a prevalence rate of 0.25-10%. Our review of the scientific literature on a radicular variant of dens in dente (RDinD) in permanent molar teeth identified only two reported cases with a confirmed diagnosis. Here, we report the third case of RDinD, in a 37-year-old woman presenting with nocturnal pain in the left maxillary second molar for 1 week. The patient had a medical history of surgery for papillary thyroid carcinoma followed by radioactive iodine therapy. We established a diagnosis of RDinD with an osteolytic lesion and transverse fracture line along the palatal root of the tooth by using cone beam computed tomography (CBCT). Extraction and periapical curettage of the lesion were performed, and the patient was followed up. In summary, we observed a rare clinical presentation of RDinD in the left maxillary second molar of a 37-year-old female patient.

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.

Molecular alterations in oral cancer using high-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue.

Loss of cell differentiation is a hallmark for the progression of oral squamous cell carcinoma (OSCC). Archival Formalin-Fixed Paraffin-Embedded (FFPE) tissues constitute a valuable resource for studying the differentiation of OSCC and can offer valuable insights into the process of tumor progression. In the current study, we performed LC-MS/MS-based quantitative proteomics of FFPE specimens from pathologically-confirmed well-differentiated, moderately-differentiated, and poorly-differentiated OSCC cases. The data were analyzed in four technical replicates, resulting in the identification of 2376 proteins. Of these, 141 and 109 were differentially expressed in moderately-differentiated and poorly differentiated OSCC cases, respectively, compared to well-differentiated OSCC. The data revealed significant metabolic reprogramming with respect to lipid metabolism and glycolysis with proteins belonging to both these processes downregulated in moderately-differentiated OSCC when compared to well-differentiated OSCC. Signaling pathway analysis indicated the alteration of extracellular matrix organization, muscle contraction, and glucose metabolism pathways across tumor grades. The extracellular matrix organization pathway was upregulated in moderately-differentiated OSCC and downregulated in poorly differentiated OSCC, compared to well-differentiated OSCC. PADI4, an epigenetic enzyme transcriptional regulator, and its transcriptional target HIST1H1B were both found to be upregulated in moderately differentiated and poorly differentiated OSCC, indicating epigenetic events underlying tumor differentiation. In conclusion, the findings support the advantage of using high-resolution mass spectrometry-based FFPE archival blocks for clinical and translational research. The candidate signaling pathways identified in the study could be used to develop potential therapeutic targets for OSCC.

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.

Haemangiopericytoma/Solitary Fibrous Tumour of Mandible: An Uncommonness in the Oral Cavity.

Among the bewildering variety of neoplasms occurring in the head and neck region, few are unique to the oral cavity which are quite challenging to diagnose. Due to the rarity of these tumours, it is the practicing oral pathologists' accountability to confirm some of these neoplasms with or without special investigative modalities to rule out the differential diagnosis histopathologically. One in the group of such tumour prevails haemangiopericytoma aka. solitary fibrous tumour (HPC/SFT). The management of these tumours is purely histopathologically driven, since the surgical procedure is dependent on the histological diagnosis. This neoplasm is histologically very difficult to confirm as benign or malignant without the use of immunohistochemical markers. We report such a rare case of a 54-year-old female patient, histopathologically confirmed diagnosis of HPC/SFT with CD34 positivity for documentation in the literature.

Assessing the analytical efficacy of TEX in diagnosing oral cancer using a systematic review approach.

The 5-year survival rates in OSCC depend on the stage at diagnosis. Patients have better survival and favourable outcomes if detected early, as compared to those diagnosed in advanced stages. Apart from biopsy and mucosal scraping examinations, exosomes from saliva and blood are emerging as an accessible source for diagnosis and providing additional information about the tumour's characteristics. Hence, the study of tumour-derived exosomal (TEX) biomarkers obtained from a liquid biopsy is emerging as a promising diagnostic tool. In this systematic review, our effort is to assess the role of TEX as a biomarker.

Revealing a rare inflammatory oral manifestation in a 6-year-old child.

A 6-year-old child with an episodic history of ulcerations over buccal mucosa was found to have severe inflammation on the palatal aspect of permanent first molars with grade 2 mobility bilaterally. Radiographical features were suggestive of bone loss around permanent molars extending to the distal aspect of the deciduous first molars. The clinical and radiographical findings were indicative of periodontal degeneration without any apparent cause visible intraorally. Further biopsy was done from the rashes present on the malar prominences, which showed nodular aggregates of atypical cells in superficial dermis. These large histiocytic cells with vesicular nuclei and nuclear grooves were immunopositive for CD1a and S100, concluding the diagnosis of Langerhans cell histiocytosis. For treatment, patient was referred to Department of Haemato-oncology and chemotherapy was suggested as per protocol.

Prevalence of methicillin resistant staphylococcus aureus isolated from saliva samples of patients with oral squamous cell carcinoma / revalencia de Staphylococcus aureus resistente a la meticilina en muestras de saliva de pacientes con carcinoma oral de células escamosas

Objectives: To study the prevalence of methicillin resistant Staphylococcus aureus (MRSA) in saliva samples of pre-surgical oral squamous cell carcinoma (OSCC) patients along with their resistance pattern to other antibiotics. Methods: Saliva samples of OSCC patients were collected and processed for isolation of MRSA. Staphylococcus aureus isolates were primarily identified using standard microbiological methods like biochemical assays, specialized media and latex agglutination test. Confirmation of MRSA strains was done by growing the isolates on MRSA agar and by using PCR to amplify two MRSA specific genes. All the isolated Staphylococcus aureus strains were subjected to antibiotic sensitivity tests. Results: A total of 17 Staphylococcus aureus strains were isolated from 50 saliva samples of pre-surgical OSCC patients of which 13 were confirmed to be MRSA. These MRSA strains were also found to be mostly resistant to other commonly used antibiotics. Univariate analysis revealed that most patients with MRSA infections had a prior history of hospitalization and surgery. Also, it was confirmed that patients with other comorbidities and infections were more prone to having MRSA present in the saliva. Conclusion: The majority of Staphylococcus aureus isolates from the saliva of OSCC patients were MRSA, and were resistant to several other commonly used antibiotics.

Objetivos: Estudiar la prevalencia de Staphylococcus aureus resistente a la meticilina (MRSA) en muestras de saliva prequirúrgicas de pacientes con carcinoma oral de células escamosas (COCE) junto con su patrón de resistencia a otros antibióticos. Métodos: Se recolectaron muestras de saliva de pacientes con COCE y se procesaron para el aislamiento de SARM. Los aislamientos de Staphylococcus aureus se identificaron principalmente mediante métodos microbiológicos estándar, como los análisis bioquímicos, los medios especializados y la prueba de aglutinación con látex. La confirmación de las cepas de SARM se realizó cultivando los aislados en agar SARM y utilizando PCR para amplificar dos genes específicos de SARM. Todas las cepas aisladas de Staphylococcus aureus se sometieron a pruebas de sensibilidad a los antibióticos. Resultados: Se aislaron un total de 17 cepas de Staphylococcus aureus a partir de 50 muestras de saliva de pacientes prequirúrgicos con COCE, de los cuales solo se confirmó que 13 eran SARM. También se encontró que estas cepas de SARM son resistentes a otros antibióticos de uso común. El análisis univariado reveló que la mayoría de los pacientes con infecciones por SARM tenían antecedentes previos de hospitalización y cirugía. Además, se confirmó que los pacientes con otras comorbilidades e infecciones eran más propensos a las infecciones por SARM. Conclusión: la mayoría de los aislamientos de Staphylococcus aureusde la saliva de los pacientes con OSCC fueron MRSA y fueron resistentes a varios otros antibióticos de uso común.

Publisher Correction: Identification of oral cancer related candidate genes by integrating protein-protein interactions, gene ontology, pathway analysis and immunohistochemistry.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Author Correction: Identification of oral cancer related candidate genes by integrating protein-protein interactions, gene ontology, pathway analysis and immunohistochemistry.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Establishing Fascin over-expression as a strategic regulator of neoplastic aggression and lymph node metastasis in oral squamous cell carcinoma tumor microenvironment.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) has an aggressive behaviour with high incidence of nodal metastasis, even in the early stages, leading to poor prognosis. For progression and metastasis of cancers, the dominant element considered is cell motility. Fascin, an actin-binding protein has emerged as a protein of general importance for a diverse set of cell protrusions with functions in cell adhesion, cell interactions, and cell migration. The role of Fascin in various carcinomas, including aggressive behaviour in OSCC has been documented, but its role as a key regulator in lymph nodes metastasis is yet to be validated. AIM: This study was piloted to evaluate and correlate Fascin expression in OSCC lymph nodes and understand the role of Fascin in contemptuous Lesional tissue, as a predictor of survival. A retrospective study designed with 40 archival OSCC cases was included as sample, 20 each of both lymph node metastasis +ve (Group 1) and -ve (Group 2) groups. All the participants were smokeless tobacco user and had tumor located at gingivo-buccal complex. RESULTS: We established that Fascin over-expression in lymph nodes were significantly associated with clinico-histopathological parameters like staging (p=0.01), tumor size (cT) (p=0.03) and differentiation; and furthermore it was highly significant in correlation to nodal status (cN) (*p≤0.001). Fascin over-expression in lymph node metastasis positive cases correlated with that of Fascin expression in contemptuous Lesional tissue signifying its role in promoting aggressive progression and metastasis. This association was found to be statistically significant (p value=0.05). Overall Survival Analysis of both lymph node metastasis +ve and -ve groups assessed by Kaplan-Meier analysis (taking death and recurrence into consideration) showed patients with high Fascin expression (in lymph node and Lesional tissue) had shorter overall survival than patients who had no to weak Fascin expression. CONCLUSION: Our findings thereby establish Fascin expression as a regulator of metastasis in OSCC tumor microenvironment and predictor of survival.

Identification of oral cancer related candidate genes by integrating protein-protein interactions, gene ontology, pathway analysis and immunohistochemistry.

In the recent years, bioinformatics methods have been reported with a high degree of success for candidate gene identification. In this milieu, we have used an integrated bioinformatics approach assimilating information from gene ontologies (GO), protein-protein interaction (PPI) and network analysis to predict candidate genes related to oral squamous cell carcinoma (OSCC). A total of 40973 PPIs were considered for 4704 cancer-related genes to construct human cancer gene network (HCGN). The importance of each node was measured in HCGN by ten different centrality measures. We have shown that the top ranking genes are related to a significantly higher number of diseases as compared to other genes in HCGN. A total of 39 candidate oral cancer target genes were predicted by combining top ranked genes and the genes corresponding to significantly enriched oral cancer related GO terms. Initial verification using literature and available experimental data indicated that 29 genes were related with OSCC. A detailed pathway analysis led us to propose a role for the selected candidate genes in the invasion and metastasis in OSCC. We further validated our predictions using immunohistochemistry (IHC) and found that the gene FLNA was upregulated while the genes ARRB1 and HTT were downregulated in the OSCC tissue samples.

Chemokines accentuating protumoral activities in oral cancer microenvironment possess an imperious stratagem for therapeutic resolutions.

Chemokines, the chemotactic cytokines have established their role in tumorigenesis and tumor progression. Studies, which explored their role in oral cancer for protumoral activity, point towards targeting chemokines for oral squamous cell carcinoma therapy. The need of the hour is to emphasize/divulge in the activities of chemokine ligands and their receptors in the tumor microenvironment for augmentation of such stratagems. This progressing sentience of chemokines and their receptors has inspired this review which is an endeavour to comprehend their role as an aid in accentuating hallmarks of cancer and targeted therapy.

Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer.

DDX3 belongs to DEAD box RNA helicase family and is involved in the progression of several types of cancer. In this work, we employed a High Throughput Virtual screening approach to identify bioactive compounds against DDX3 from ZINC natural database. Ketorolac salt was selected based on its binding free energy less than or equals to -5 Kcal/mol with reference to existing synthetic DDX3 inhibitors and strong hydrogen bond interactions as similar to crystallized DDX3 protein (2I4I). The anti-cancer activity of Ketorolac salt against DDX3 was tested using oral squamous cell carcinoma (OSCC) cell lines. This compound significantly down regulated the expression of DDX3 in human OSCC line (H357) and the half maximal growth inhibitory concentration (IC50) of Ketorolac salt in H357 cell line is 2.6 µM. Ketorolac salt also inhibited the ATP hydrolysis by directly interacting with DDX3. More importantly, we observed decreased number of neoplastic tongue lesions and reduced lesion severity in Ketorolac salt treated groups in a carcinogen induced tongue tumor mouse model. Taken together, our result demonstrates that Ketorolac salt is a newly discovered bioactive compound against DDX3 and this compound can be used as an ideal drug candidate to treat DDX3 associated oral cancer.