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Oral Surg Oral Med Oral Pathol Oral Radiol. 2018 Jun;125(6):650-669. doi: 10.1016/j.oooo.2018.03.012. Epub 2018 Apr 4.

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications.

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Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece. Electronic address:
Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Italy.
Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Greece.
Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Canada.
Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, Connecticut, USA.
Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, USA.
Department of Pathology, The University of Chicago, Illinois, USA.
Pathology, Surgical and Hospital Dentistry, University of Louisville, USA.


Identification and management of potentially premalignant oral epithelial lesions (PPOELs) at highest risk of malignant transformation holds great promise for successful secondary prevention of oral squamous cell carcinoma, potentially reducing oral cancer morbidity and mortality. However, to date, neither clinical nor histopathologic validated risk predictors that can reliably predict which PPOELs will definitively progress to malignancy have been identified. In addition, the management of PPOELs remains a major challenge. Arguably, progress in the prevention and treatment of oral premalignancy and cancer will require improved understanding of the underlying molecular mechanisms, facilitating the discovery of diagnostic, prognostic, and predictive markers, as well as the identification of novel targeted therapeutics. This review provides a synopsis of the molecular biomarkers that have been studied in PPOELs and have been correlated with the presence and grade of dysplasia and/or their propensity to undergo malignant transformation to oral squamous cell carcinoma. The emphasis is on highlighting new emerging research fields, particularly epigenetic events, including methylation and micro-RNA regulation. Several promising biomarkers are highlighted. Current limitations and challenges are discussed. Recommendations for future focused research areas, to validate and promote clinically useful applications, are offered.

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