Prognostic Significance of ALDH1, Bmi1, and OCT4 Expression in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

BACKGROUND: Increasing evidence suggests the involvement of cancer stem cells (CSCs) in both oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Among the various CSC markers, aldehyde dehydrogenase (ALDH) 1, B cell-specific Moloney murine leukaemia virus integration site 1 (Bmi1), and octamer-binding protein 4 (OCT4) have been noted to increase in OSCC. The aim of the study was to analyze ALDH1, Bmi1, and OCT4 expression in OED and OSCC with clinicopathologic correlation and survival analysis. METHODS: A total of 40 cases each of OED and OSCC were retrieved from departmental archives. Expression of ALDH1, Bmi1, and OCT4 was analyzed using immunohistochemistry and was correlated with clinicopathological parameters. A follow-up ranging from 6 to 52 months was considered for Kaplan-Meier survival analysis. The log-rank test was performed to analyze significant difference in survival rates. RESULTS: The expression levels of ALDH1, Bmi1, and OCT4 increased significantly from OED through OSCC (P < .05). The expression of ALDH1 and OCT4 showed a significant correlation with lymph node metastasis. Positive cases of ALDH1 showed a significantly reduced survival rate compared to cases showing negative expression. Kaplan-Meier survival analysis showed a significant reduction of survival rate (P = .00) in patients showing a positive expression for all the 3 markers. CONCLUSION: ALDH1 and OCT4 could be used as individual prognostic markers for assessing prognosis. ALDH1, Bmi1, and OCT4 could be used as a collective panel of markers to enable surgeons in predicting the prognosis of patients and thereby carry out prompt follow-up for such cases.

Expression of hTERT in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma - an Immunohistochemical Analysis.

Human telomerase reverse transcriptase enzyme, the catalytic subunit of telomerase are seen to be frequently reactivated in cancers including Oral squamous cell carcinoma (OSCC). Increased hTERT expression have been seen in potentially malignant conditions including Oral submucous fibrosis (OSMF). The aim of the study was to evaluate the expression levels in OSMF, OSCC in the background of OSMF and OSCC using immunohistochemistry and also to correlate hTERT expression with clinicopathologic parameters. A total of 50 histopathologically diagnosed cases of 20 OSMF, 20 OSCC wherein 5 were OSCC in the background of OSMF and 10 Normal oral mucosae were retrieved from the departmental archives and subjected to immunohistochemical analysis of hTERT. The expression of hTERT increased from normal, OSMF, to OSCC with statistically significant differences in mean labelling score (LS). We also found a shift in cellular localization of stain where, normal mucosal tissues showed a nuclear stain unlike OSMF, where combined nuclear and cytoplasmic staining as noted. The tumor cells in OSCC showed predominant cytoplasmic staining. There was no correlation between hTERT expression and clinicopathological parameters of OSMF. However, a significant increase of hTERT expression was seen with increasing histological grading of OSCC. These results suggest the role of hTERT in the early event of malignant transformation of OSMF. Telomerase could be used as a potent diagnostic marker to identify high-risk group of OSMF.

Biomarkers in Tumorigenesis Using Cancer Cell Lines: A Systematic Review

Cancer is a leading cause of death worldwide. Despite many research advancements in the field, the genetic changes regulating the transformation of normal oral cells into malignant cells have not been fully elucidated. Several studies have evaluated carcinogenesis at the molecular level. Cancer cell lines are commonly used in biomedical research because they provide an unlimited source of cells and represent various stages of initiation and progression of carcinogenesis in vitro. Aims: The objective of the study was to review original research articles using cancer cell lines as a tool to understand carcinogenesis and to identify the genes involved in tumor development. Additionally, we also examined the application of the genes as predictive biomarkers. Methods and Materials: Several databases, including PubMed, Google Scholar, Ebsco, and Science Direct, were searched from 1985 to December 2016 using various combinations of the following key words: "mouth neoplasm", "cell lines", and "tumorigenesis". Original experimental studies published in English were included. We excluded letters to the editor, historic reviews, and unpublished data from the analysis. Results: There were 17 studies (in vitro) included in the analysis. There were 14 genes and 4 miRNAs involved in malignant transformation of oral keratinocytes into cancer cells. The most commonly studied genes were p53, cyclin D1, and hTERT. Conclusion: Additional reviews and studies are needed to identify a panel of genes specific to various potentially malignant disorders and to aid in the early detection of oral squamous cell carcinoma (OSCC) because tumorigenesis involves the mutation of multiple genes. Furthermore, improving advanced cost-effective diagnostic methods may benefit the public health sector.