Oral Potentially Malignant Disorders (OPMD) are that category of heterogenous mucosal lesions of oral cavity, which when compared to their normal and other diseased counterparts, are prone to have increased probability/ risk of transformation to malignancy i.e. Oral Squamous Cell Carcinoma (OSCC). (1) This term was coined for the first time in the year 2007 following an expert meeting conducted by WHO (World Health Organization) Collaborating Centre for Oral Cancer and thereafter this term was included in 4th Edition of WHO Classification of Head and Neck Tumours. (2) The overall worldwide prevalence of OPMDs is considered to be 4.5%, on an average, due to wide differences in the not only the geographical terrains, but also the variety of cultural norms and tradition people follow across the globe. (3) The lesions included in this category are Oral Leukoplakia, Erythroplakia, Oral Lichen Planus, Lichenoid reactions and Proliferative Verrucous Leukoplakia. Each of these lesions named have their own characteristic clinical, histologic characteristics and transformation percentage through which they can be identified and diagnosed. (4) Once diagnosed, they pose a clinical challenge because of the intrinsic potential to develop into OSCC, and for this reason proper follow-up and therapies should be considered for them. So, for a proper follow-up and continued monitoring of such lesions, a common marker which could be applied on the tissues presents itself in results microscopically in such a way that is not only precise and accurate for the prediction of transforming rate, but also draws instant attention to the lesion to halt the progression and prevent further morbidity and financial constraints.
In addition to their characteristic histopathological features, some features of dysplasia may or may not be found associated with them, and when it occurs, it is often found in erythroplakia. Oral Epithelial Dysplasia (OED) is a histopathological term provided when the cells morphological and architectural pattern is deranged as compared to that of normal mucosal cells. (5) WHO has classified them on the basis of severity of derangement into Mild, Moderate and severe dysplasia. (6) The presence of a dysplastic area in a tissue always increases the chances of malignant transformation, although the rate of transformation is of varied percentage reported in literature. (7)
Head and neck squamous cell carcinoma (HNSCC), also referred to as OSCC is an epithelial neoplasm which arises either directly as a result of exposure to various environmental factors or may arise from OPMDs or associated dysplasia. (8) Carcinogenesis is a multi-step, multi-gene, and multi-stage complex process involving the oncogene activation and inactivation of tumour suppressor genes. (9) Thereby, not only knowing the causative agent and the genes is important for diagnosis, but also the molecular pathogenesis and the protein formation underlying disease progression is important, which would help not only in knowing the disease process, but also to identify and prevent the disease beforehand to improve patient’s life outcomes.
Tumour suppressor genes (TSGs) are those genes that prevent a cell during its replication to transform into a cancerous cell. These genes are always in balance with the tumour promoter gene, to keep a check on cycle. However, if these TSGs gets mutated or suffers a loss of function, the cell may be relieved of its controlled proliferation and therefore, would lead to cancer initiation. (10) A lot of TSGs have been analysed and extensively studied in literature. One such gene that this pilot study has taken into consideration in case of OSCC and OPMD is BRAC2 gene. This is a TSG gene, which corresponds its location to chromosome 13q12–
13 (Wooster et al., 1995). Germline mutation in this gene is responsible for large proportion of cases of hereditary breast cancer families, but it has also been seen in association with OSCC.
Therefore, this pilot study aims to analyse the expression of BRCA2 gene in oral tissue samples which has been diagnosed under different grades of OSCC as well as OPMDs. This is first amongst its types to analyse the expression in both the cases combined, which can add to whether this gene plays a role in both cancer and dysplastic cells.