Epithelial-mesenchymal transition in cancer stem cells: Therapeutic implications.

Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs may generate tumors through the processes of self-renewal and differentiation into multiple cell types. CSCs present in tumors are normally resistant to conventional therapy and may contribute to tumor recurrence. Tumor residuals present after therapy, with CSCs enrichment, have all the hallmarks of epithelial-mesenchymal transition (EMT). In this review, we discuss the relationship between EMT and CSCs in cancer progression and its therapeutic implications in oral squamous cell carcinoma.

Evaluation of salivary MMP-9 in oral squamous cell carcinoma and oral leukoplakia using ELISA.

Background: Cancer of the lip and the oral cavity is collectively the sixth most common malignancy worldwide, out of which 90% are oral squamous cell carcinomas (OSCCs). Oral cancer survival rates depend mainly upon the stage in which it is diagnosed. Successful early detection would eventually increase the survival rate. OSCCs may be preceded by potentially malignant disorders (PMDs) that are characterised by visible clinical changes in the oral mucosa. Correct diagnosis and timely treatment of PMDs may help prevent malignant transformation in oral lesions. Oral leukoplakia (OL) is the best known potentially malignant disorder of the oral mucosa with a malignant transformation rate of about 3% to 33%. Tumour markers in saliva have emerged as a new diagnostic tool in the early detection of oral cancer. Matrix metalloproteinase 9 (MMP-9) is a gelatinase which plays an important role in tumourogenisis. The present study was done to evaluate the salivary levels of MMP-9 in OSCC and oral leukoplakia patients using enzyme-linked immunosorbent assay (ELISA). Materials and Methods: The study was conducted among 102 subjects, which included 34 OSCC patients (group I), 34 OL patients (group II), and 34 healthy subjects (group III). Unstimulated saliva was collected by the passive drooling method from all the study subjects during the study period, centrifuged, and stored at -80°C. The salivary MMP-9 was estimated in mg/ml using the sandwich ELISA technique. The data were analysed using a statistical software package, EZR. One-way analysis of variance was used for the comparison of salivary MMP-9 levels in OSCC, OL, and normal oral mucosa. Scheffe's multiple comparison was carried out to compare salivary MMP-9 levels among the different histological grades of OSCC and oral epithelial dysplasia. For all statistical interpretations, P ≤ 0.0 was considered the threshold for statistical significance. Results and Conclusion: The mean salivary MMP-9 level in OSCC, OL, and normal oral mucosa was 50.9 ± 5.7 ng/ml, 31.6 ± 6 ng/ml, and 16.2 ± 4.8 ng/ml, respectively. Patients with OSCC had significantly higher levels of salivary MMP-9 when compared to OL and normal mucosa. Higher levels of salivary MMP-9 were observed in poorly differentiated OSCC when compared to well and moderately differentiated OSCCs. The salivary MMP-9 was higher in severe oral epithelial dysplasia when compared to mild and moderate oral epithelial dysplasias. As malignant transformation rates are higher in patients with severe oral epithelial dysplasia when compared to mild and moderate oral epithelial dysplasia, salivary MMP-9 could be considered as a surrogate marker of malignant transformation.

Chondrosarcoma of the maxilla in a young female: A case report.

ABSTRACT: Sarcomas of the head and neck region are rare tumors, constituting less than 1% of malignant neoplasms in this area. Approximately 20% of these sarcomas originate from bone or cartilage. Chondrosarcomas are malignant mesenchymal tumors showing cartilaginous differentiation. These tumors usually show a predilection to the male gender and occur commonly in the older age group. Here, we report a case of chondrosarcoma of the anterior maxilla in a young female.

Immunohistochemical evaluation of galectin-3 expression in oral squamous cell carcinoma, oral leukoplakia and normal mucosa.

Background: Galectin 3 (Gal-3) has diverse functions critical in cancer biology including cell proliferation, apoptosis, evasion of immune responses and angiogenesis. The expression of Gal-3 is heterogeneous in normal and neoplastic tissues. In oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL), both increased and decreased expressions of Gal-3 were elicited in numerous studies. Aims: To evaluate, compare and correlate the immunohistochemical expression of Gal-3 in OSCC, OL and normal oral mucosa. Settings and Design: The study was conducted at the Department of Oral Pathology and Microbiology at PMS College of Dental Science and Research, Vattapara, Thiruvananthapuram. This is a retrospective analytical study. Methods and Material: Clinically diagnosed and histopathologically confirmed cases of OSCC (n = 21), OL (n = 21), and normal oral mucosa (n = 21) were included in the study. Paraffin-embedded tissues were subjected to immunohistochemical analysis for Gal-3 expression. Gal-3 staining expression, staining distribution and cellular localisation were evaluated. All sampled categories were compared using immunohistochemical scoring analysis such as the H-score, labelling index (LI), immunoreactive score (IRS) and staining intensity (SI). Statistical Analysis: The results were statistically analysed using multivariate analysis of variance (MANOVA) within and among the groups. Results and Conclusion: The statistical inferences obtained found that the H-score could be used as a guideline for better differentiation between the groups and among the groups. The P value obtained was < 0.0125 and was found to be significant. The observation in our study shows that the immunohistochemical expression of Gal-3 gradually decreased from normal oral mucosa to OL to OSCC.

Evaluation of aryl hydrocarbon receptor expression in oral squamous cell carcinoma and normal oral mucosa using western blot.

BACKGROUND: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that acts as a binding site for toxic chemicals, particularly the dioxin group of chemicals. Elevated levels of AHR have been observed in various human cancers, including lung carcinomas, hepatic carcinomas and in mammary tumors. However, the expression of AHR in oral squamous cell carcinoma (OSCC) patients who are tobacco users are less explored. AIMS AND OBJECTIVES: The aim of the present study is to evaluate and compare AHR levels in OSSC patients and in normals using Western blot technique in an attempt to explore the possible role of AHR in oral carcinogenesis. MATERIALS AND METHODS: The study sample consisted of ten oral squamous cell carcinoma cases which were diagnosed clinically and confirmed histopathologically as OSCC and four samples of the normal oral mucosa. AHR protein expression was evaluated using Western blot technique and chemiluminescence detection kit. The densitometry was performed on a Microtek scan maker MSP flatbed scanner and quantified using Image J software. Mean AHR protein levels were calculated and compared between OSCC and normal oral mucosa using Student's t-test. RESULTS: The mean AHR protein level in OSCC samples (n = 10) was 2878.90 ± 1231.27 and 975.75 ± 227.27 in the normal oral mucosa (n = 4). The OSCC samples showed significantly higher levels of AHR protein compared to the normal oral mucosa (P = 0.008). CONCLUSION: The study showed a significantly higher expression of AHR in oral squamous cell carcinoma samples when compared to the normal oral mucosa, suggesting a possible role of AHR in the initiation, promotion and progression of oral squamous cell carcinoma.

Expression of transmembrane protein aquaporin-3 in oral epithelial dysplasia and oral squamous cell carcinoma.

OBJECTIVES: The objective of this study was to evaluate aquaporin-3 (AQP3) expression in patient samples of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC), thereby assessing the potential of AQP3 as a molecular marker for tumor progression. STUDY DESIGN: An in vitro comparative study was done to determine the AQP3 expression on 20 surgical biopsy specimens each of OED and OSCC using immunohistochemistry. Twenty specimens of normal oral mucosa were kept as controls. The results were statistically analyzed using one-way analysis of variance and post hoc analysis. RESULTS: The expression of AQP3 was analyzed and further semiquantified using H-scores. The mean H-score showed a statistically significant difference between OSCC, OED, and normal oral mucosa (P < .05). There was a significant increase in the expression of AQP3 in OSCC and OED compared to normal oral mucosa. The highest expression was observed in OSCC (P < .01). CONCLUSION: The observations of the study indicate that staining intensity of AQP3 increased from dysplastic noninvasive lesion to invasive OSCC, suggesting a possible role of AQP3 as a biomarker for tumor progression.

Epithelial-mesenchymal transition in oral squamous cell carcinoma: An insight into molecular mechanisms and clinical implications.

Epithelial-mesenchymal transition (EMT) is an important event in embryonic development, fibrosis and cancer invasion. During cancer progression, the activation of EMT permits cancer cells to acquire migratory, invasive and stem-like properties. Despite recent advances in treatment, there is no improvement in the 5-year overall survival rate of oral squamous cell carcinoma (OSCC). Local recurrence and lymph node metastasis are considered to be mainly responsible for the low survival rate in OSCC. EMT plays a major role in local recurrence and lymph node metastasis of oral cancer. This review article addresses the clinical implications of EMT in OSCC and explains the molecular mechanisms of EMT, highlighting the cadherin switching and signaling pathways involved.

Cancer stem cells: A comprehensive review on identification and therapeutic implications.

Cancer stem cells (CSCs) are distinct subpopulations of tumor cells that possess the ability for perpetual self-renewal and proliferation. They produce downstream progenitor cells and cancer cells that drive tumor growth. Studies of many cancer types including oral squamous cell carcinoma (OSCC) have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple CSC subtypes within OSCC, making investigation reliant on the use of multiple markers. This review paper focuses on the current knowledge in CSC markers including OCT4, SOX2, NANOG, aldehyde dehydrogenase 1, CD44, CD24, CD133 and Musashi-1, highlighting their use and validity in OSCC CSC research.

Immunohistochemical detection of p53 and p63 in oral squamous cell carcinoma, oral leukoplakia, and oral submucous fibrosis.

AIM: Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant disorders such as leukoplakia and oral submucous fibrosis (OSF). p63 in concert with p53 regulates cell proliferation and differentiation and may have a role in potentially malignant and malignant lesions of the oral cavity. The aim of the study was to evaluate and compare the expression of p53 and p63 proteins in OSCC, leukoplakia, and OSF by immunohistochemistry (IHC). METHODS: Tissue sections of OSCC (n = 20), leukoplakia (n = 20), OSF (n = 20) and normal oral mucosa (n = 10) were stained with p53 and p63 antibodies by IHC. Mean labeling index (LI) among the study groups were compared using the Kruskal-Wallis test. RESULTS: The mean LI of p53 for OSCC, leukoplakia, OSF, and normal mucosa were 56.9 ± 21.3, 37.6 ± 12.6, 34.6 ± 8.7 and 15.1 ± 9, while mean LI of p63 were 56.8 ± 19.6, 42.3 ± 10.5, 32.8 ± 12.1, and 26.4 ± 9.4. The mean LI of p53 and p63 were significantly higher in OSCC, leukoplakia and OSF compared to normal mucosa (P < 0.01; P < 0.01). CONCLUSION: The significant increase in expression of p53 and p63 proteins in OSCC, leukoplakia, and OSF suggests their role as surrogate markers of malignant transformation.