Exosomes: Mediators of cellular communication in potentially malignant oral lesions and head and neck cancers.

Exosomes are a unique type of extracellular vesicles that contain a plethora of biological cargo such as miRNA, mRNA, long non-coding RNA, DNA, proteins and lipids. Exosomes serve as very effective means of intercellular communication. Due the presence of a lipid bilayer membrane, exosomes are resistant to degradation and are highly stable. This makes them easily identifiable in blood and other bodily fluids such as saliva. The exosomes that are secreted from a parent cell directly release their contents into the cytoplasm of a recipient cell and influence their cellular activity and function. Exosomes can also transfer their content between cancer cells and normal cells and regulate the tumor microenvironment. Exosomes play a vital role in tumor growth, tumor invasion and metastasis. Exosomes provide a multitude of molecular and genetic information and have become valuable indicators of disease activity at the cellular level. This review explores the molecular characteristics of exosomes and the role that exosomes play in the tumorigenesis pathway of potentially malignant oral lesions and head and neck cancers The application of exosomes in the treatment of oral cancers is also envisioned. Exosomes are very small and can easily pass through various biological barriers, making them very good delivery vectors for therapeutic drugs as well as to selectively induce DNA's mRNA and miRNAs into targeted cancer cells.

Non-familial paediatric oral myofibroma - A masquerade. Case report with a brief literature review.

Myofibromas are fibrous tumours that could be of familial or non-familial origin, belonging to the fibroblastic and myofibroblastic subset with a wide spectrum of clinical behaviour. Oral myofibromas present with a broad range of differential diagnoses, including benign and malignant lesions. Histopathologically, these lesions may imitate many other soft tissue tumours of the oral cavity, such as spindle cell tumours of nerve, smooth muscle cell origin, and other myofibroblastic lesions, thus leading to misdiagnosis and mistreatment. In the present paper, we report a soft tissue lesion, which presented as a growth on the gingivobuccal sulcus in a 7-year-old child. We also emphasise the various differential diagnoses that need to be eliminated and the importance of immunohistochemistry to know the nature of tumour cells in establishing the accurate diagnosis.

Expression of Fascin and SALL4 in odontogenic cysts and tumors: an immunohistochemical appraisal.

Background: Various stemness markers (SOX2, OCT4, and NANOG) have been studied in odontogenic cysts and tumors. However, studies on SALL4 having similar properties of stemness has not been documented. Additionally, insight into fascin as a migratory molecule is less explored. In this study, the expression of SALL4 and fascin were evaluated in ameloblastoma, adenomatoid odontogenic tumor (AOT), odontogenic keratocyst (OKC), dentigerous cyst (DC), radicular cyst (RC), and calcifying odontogenic cyst (COC). Methods: Semi-quantitative analysis of fascin and SALL4 immuno-positive cells was done in a total of 40 cases of ameloblastoma (11 plexiform, 12 follicular, 12 unicystic, and 5 desmoplastic) variants, 6 cases of AOT, 15 each of OKC, DC, RC and 5 of COC. Chi-square test was applied to evaluate the association between SALL4 and fascin expression in odontogenic cysts and tumors. Results: Fascin immunopositivity was observed in peripheral ameloblast-like cells, and the expression was weak or absent in stellate reticulum-like cells. A moderate to weak immune-reactivity to SALL4 was observed in the cytoplasm of ameloblastoma, epithelial cells of dentigerous and radicular cysts, having a marked inflammatory infiltrate, which was an interesting observation. COC and AOT had negative to weak expressions. No recurrence has been reported. Conclusions: Expression of fascin in ameloblastomas elucidate their role in motility and localized invasion. Its expression in less aggressive lesions like DC, COC, AOT will incite to explore the other functional properties of fascin. SALL4 expression in the cytoplasm of odontogenic cysts and tumors may represent inactive or mutant forms which requires further validation.

Elucidating the role of excision repair cross-complement group 1 in oral epithelial dysplasia and early invasive squamous cell carcinoma: An immunohistochemical study.

OBJECTIVES: Oral epithelial dysplasia (OED) is characterized by cellular alterations which have the proclivity of progressing to squamous cell carcinoma. Excision repair cross-complement group 1 (ERCC1) is one of the key proteins involved in nucleotide excision repair (NER) pathway. The expression of ERCC1 has been studied in colorectal, esophageal, ovarian and oral squamous cell carcinoma; but, very few studies have been done to apprehend the expression of ERCC1 in OED and early invasive squamous cell carcinoma (EISCC). The goal of this study is to evaluate the role of ERCC1 in OED and EISCC. MATERIALS AND METHODS: Histopathologically diagnosed cases of moderate dysplasia (n = 10), severe dysplasia (n = 10) and EISCC (n = 10) were retrieved. 4 µ thick sections were cut from the formalin-fixed paraffin-embedded tissue blocks. The sections were immunohistochemically stained for ERCC1 following standard protocols. The expression of ERCC1 was evaluated semiquantitatively. Statistical analysis was carried out using Fischer's exact t-test. RESULTS: The expression of ERCC1 was found to be strong (+3) in EISCC, moderate (+2) in severe dysplasia and mild (+1) in moderate dysplasia. Thus, the results were statistically significant between the three groups (P < 0.001). CONCLUSION: Disruption in the mechanisms that regulate cell cycle checkpoints and DNA repair mechanism results in genomic instability; these alterations might contribute to carcinoma. ERCC1 is essential to repair the DNA damage induced by various carcinogens. The present study shows significant difference in the expression of ERCC1 between EISCC and OED, which suggests ERCC1 could be used as one of the predictive markers.

Spalt-like transcription factor 4 expression in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical appraisal.

BACKGROUND: Spalt-like transcription factor 4 (SALL4) is a stem cell marker that plays a critical role in maintaining the pluripotency and self-renewal of embryonic and hematopoietic stem cells. Only a few studies have been done to apprehend the expression of SALL4 in the potentially malignant oral lesion (leukoplakia with dysplasia) and oral squamous cell carcinoma (OSCC). AIM: The aim of this study is to evaluate the expression of SALL4 in leukoplakia with dysplasia and OSCC and to correlate the expression of the marker (SALL4) with the various clinicopathological parameters and patient outcome. MATERIALS AND METHODS: Immunohistochemistry for SALL4 protein was performed on 140 cases: those histopathologically confirmed cases of leukoplakia with dysplasia (n = 30) and OSCC (n = 110). Ten cases of nonepithelial neoplasm (fibroepithelial hyperplasia and excised tissue surrounding impacted third molars) were taken as control. Statistical analyses were applied to evaluate correlations between SALL4 overexpression and clinicopathological features of leukoplakia and OSCC. Survival rates were analyzed using Kaplan-Meier method. RESULTS: SALL4 positivity was observed to be higher (P = 0.001) in the tumor cells of OSCC with Immuno Reactive Score (IRS) ranging from 0 to 9. Poorly differentiated squamous cell carcinoma (SCC) had paramount higher expression with a median IRS of 6. Similar IRS and above (IRS, 6-9) was observed in Stage I (five cases), which recurred and well-differentiated cases with metastasis (four cases) while in leukoplakia with dysplasia the SALL4 expression was weak with a range of 2-4. CONCLUSIONS: SALL4 being one of the cancer stem cell molecules plays an important role in the progression of oral cancer, which was evident in this study. This could also account for aggressive clinical behavior. Follow-up of these patients would relate this molecule could be responsible for cancer relapse. Patients diagnosed to have oral epithelial dysplasia had a low expression of SALL4, are under follow-up, although seven cases did transform to SCC. Thus, we conclude, SALL4 may be of prognostic relevance, but in oral epithelial dysplasia, it requires further investigations.

Paediatric unicystic ameloblastoma - A report of 2 cases.

Unicytic ameloblastoma is a variant of ameloblastoma encompassing about 6% of ameloblastomas. They represent cystic lesions that reveal clinical and radiographic features of a cyst, but the histopathological features demonstrate a typical ameloblastomatous epithelium lining the cyst. Plexiform unicystic ameloblastoma, a variant of unicystic ameloblastoma refers to the pattern of proliferation where one or more nodules of ameloblastomatous epithelium project from the cystic lining into the lumen demonstrating an edematous plexiform pattern. The lesion is seen more commonly in the third and fourth decades of life with less than 10% of cases being reported in the first decade. Here, we report two cases of unicystic ameloblastoma in paediatric patients. This report also aims to provide an insight on the pathogenesis and treatment aspects of this distinct entity.

Odontogenic cysts and odontogenic tumors in a large rural area from India. A 10-year reflection.

OBJECTIVES: To determine the prevalence of odontogenic cysts and tumors along with age range, sex distribution, site of presentation and also to identify the most common type of odontogenic cyst and tumor among the population of coastal Karnataka over a 10-year period. METHODS: Data was collected from patient records and histologically diagnosed cases of odontogenic cysts and tumors. The age, gender of patients, as well as the site of lesion was recorded. RESULTS: A total of 167 cases were retrieved. Among them, 125 cases were diagnosed as odontogenic cysts and 42 cases were odontogenic tumors. Radicular cyst was the most frequently diagnosed cyst and unicystic ameloblastoma was the most frequently diagnosed tumor. A strong predilection for males was observed for both the odontogenic cysts and odontogenic tumors. Odontogenic cysts were more commonly seen in individuals in the age range 21-41 years, while odontogenic tumors were frequently seen in individuals in the age range 1-20 years. CONCLUSION: This study provides an epidemiological profile of odontogenic cysts and odontogenic tumors among a rural population of coastal Karnataka. There is a notable variation in demographic profile of odontogenic cysts and odontogenic tumors in this population when compared with other populations.

Omics data-driven analysis identifies laminin-integrin-mediated signaling pathway as a determinant for cell differentiation in oral squamous cell carcinoma.

BACKGROUND: In recent years, high-throughput omics technologies have been widely used globally to identify potential biomarkers and therapeutic targets in various cancers. However, apart from large consortiums such as The Cancer Genome Atlas, limited attempts have been made to mine existing datasets pertaining to cancers. METHODS AND RESULTS: In the current study, we used an omics data analysis approach wherein publicly available protein expression data were integrated to identify functionally important proteins that revealed consistent dysregulated expression in head and neck squamous cell carcinomas. Our analysis revealed members of the integrin family of proteins to be consistently altered in expression across disparate datasets. Additionally, through association evidence and network analysis, we also identified members of the laminin family to be significantly altered in head and neck cancers. Members of both integrin and laminin families are known to be involved in cell-extracellular matrix adhesion and have been implicated in tumor metastatic processes in several cancers. To this end, we carried out immunohistochemical analyses to validate the findings in a cohort (n = 50) of oral cancer cases. Laminin-111 expression (composed of LAMA1, LAMB1, and LAMC1) was found to correlate with cell differentiation in oral cancer, showing a gradual decrease from well differentiated to poorly differentiated cases. CONCLUSION: This study serves as a proof-of-principle for the mining of multiple omics datasets coupled with selection of functionally important group of molecules to provide novel insights into tumorigenesis and cancer progression.

Giant-cell fibroma: Understanding the nature of the melanin-laden cells.

Giant-cell fibroma is a localized, benign fibrous mucosal mass, which clinically mimics any other fibroepithelial growth, and its distinction from other lesions is on the basis of its peculiar histopathology. A case of giant-cell fibroma with stroma strewn with brown pigment-laden cells is presented herewith. Immunohistochemical staining aided with histochemical reaction to understand the origin of these cells was carried out. Various mechanisms that explain the presence of melanin granules in reactive lesions of giant-cell fibroma is discussed in the present report.