Profiling Expression of Brac2 Gene in Cases of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders-a Pilot Study.

Profiling Expression of Brac2 Gene in Cases of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders-a Pilot Study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Profiling Expression of Brac2 Gene in Cases of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders-a Pilot Study. ARUSHI -, Hrithik jain This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4733804/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Oral Potentially Malignant Disorders (OPMD) are 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). Once diagnosed, they pose challenge because of the intrinsic potential to develop into OSCC. 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. Carcinogenesis is a multi-step, multi-gene, and multi-stage complex process involving the oncogene activation and inactivation of tumour suppressor genes. Thereby, not only knowing 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. Thereby, this study identified the expression of tumour suppression gene (TSG), BRAC2 gene, in cases of both OSCC and OPMDs. The results showed that with increased grade and severity of the lesion, the expression of this gene was not seen in either category of the lesions. Thereby, we conclude that a large no of sample size study would be the need to confirm the findings. Health sciences/Biomarkers Biological sciences/Cell biology OSCC OPMD TSG BRCA2 gene. Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION 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. MATERIAL AND METHOD 2.1 Tissue samples The data of the diagnosed cases of both OPMDs as well as cases of OSCC in different grading stages were obtained from the archives. The diagnosis was reviewed and confirmed by two oral pathologists after retrieving the histopathological slides from the archives. Their respective formalin-fixed, paraffin-embedded (FFPE) samples were obtained from the archives of the Department and were then sent for immune-histochemical analysis. The tissue retrieval from the archives along with the information was obtained following the guidelines and approval from the institution. All the procedures have been performed following standard protocols. 2.2. Immunohistochemical Procedure All immunohistochemical stains were performed on tissue sections (4 micrometre thickness) prepared from formalin-fixed (4% neutral buffered formalin) paraffin-embedded tissue blocks. The sections were de-paraffinized in xylene and rehydrated through a series of graded alcohols. The endogenous peroxidase activity was blocked for 30 minutes in a solution containing 0.3% hydrogen peroxide. Antigen retrieval was performed using pressure method by putting the slides for 30 minutes. After antigen retrieval, the specimens were allowed to cool for 30 minutes and were then incubated at 4ºC overnight with the indicated primary antibodies. The diluted and used indicated antibodies were: BRCA2 (1:100, clone MS-13, Abcam, Cambridge, USA). After an overnight incubation with the primary antibody, the slides were incubated with post-primary solution for 30 minutes and were then incubated with the polymer for 30 minutes. The reactions were developed with diaminobenzidine (DAB), followed by Mayer’s haematoxylin counterstaining. The slides were then dehydrated in a graded series of ethanol and mounted using mountant which were then ready to be observed under microscope. The positive control to compare the staining of the tissues was that of breast cancer. All immunohistochemistry evaluation and analysis were carried out blinded to the patients’ clinical outcomes. All the stained slides were then scanned using Zeiss Penta head and then the identification of the positive staining reaction was visualised as brown colour inside the nucleus which was identified and confirmed by two separate pathologists. Faint diffuse staining, isolated nuclear staining, weak staining of single interspersed cells or noise noted were scored negative and these cells were kept out of the annotation area. Next, to quantify and provide a mean expression percentage and a specific score for every case, the MagCam was attached to the microscope and QuPath-0.5.1 software was used for annotating the positive-stained cells and the expression percentage was taken for each case. The mean was taken after analysing the annotations from five separate High Power Fields (HPF). 2.3. Statistical Analysis For the statistical analysis, all acquired results were documented and evaluated using Microsoft excel. The mean expression percentage was calculated using SPSS software version 20.0.0. and then the IHC score was provided as per the scoring given by Bondarenko et al. 11 To prevent interpreting errors, the IHC slides were assessed by two reviewers who were blinded to the diagnostic data obtained from the archives. Results Immunohistochemical Findings Mean expression percentage and the respective IHC scores are documented for each case of OSCC and OPMD and are collectively presented in Table 1 in separate sub-tables. For cases of potentially malignant disorders taken into account, only cases of mild dysplasia has shown positive expression in nucleus in lower one-third of the epithelium, whilst rest of the cases did not show any expression. Table 1 REPRESENTING AVERAGE IHC SCORES IN CASES OF ORAL POTENTIALLY MALIGNANT DISORDERS FOR EXPRESSION OF BRCA2 GENE S.NO. DIAGNOSIS IHC SCORE (AVERAGE) 1. MILD DYSPLASIA 1 2. MILD DYSPLASIA 4 3. MILD DYSPLASIA 0 4. MODERATE DYSPLASIA 0 5. SEVERE DYSPLASIA 0 6. LICHEN PLANUS 0 7. LICHEN PLANUS 0 8. LICHEN PLANUS 0 9. ORAL SUBMUCOUS FIBROSIS 0 Table 2 REPRESENTING AVERAGE IHC SCORES IN CASES OF ORAL SQUAMOUS CELL CARCINOMA FOR EXPRESSION OF BRCA2 GENE S.NO. DIAGNOSIS IHC SCORE (AVERAGE) 1. WELL-DIFFERENTIATED SCC 0 2. WELL-DIFFERENTIATED SCC 2 3. WELL-DIFFERENTIATED SCC 3 4. WELL-DIFFERENTIATED SCC 0 5. WELL-DIFFERENTIATED SCC 2 6. MODERATELY-DIFFERENTIATED SCC 0 7. MODERATELY-DIFFERENTIATED SCC 0 8. MODERATELY-DIFFERENTIATED SCC 0 9. MODERATELY-DIFFERENTIATED SCC 0 10. MODERATELY-DIFFERENTIATED SCC 0 11. MODERATELY-DIFFERENTIATED SCC 3 12. MODERATELY-DIFFERENTIATED SCC 0 13. MODERATELY-DIFFERENTIATED SCC 0 14. MODERATELY-DIFFERENTIATED SCC 0 15. MODERATELY-DIFFERENTIATED SCC 0 16. MODERATELY-DIFFERENTIATED SCC 0 17. POORLY-DIFFERENTIATED SCC 0 18. POORLY-DIFFERENTIATED SCC 0 19. POORLY-DIFFERENTIATED SCC 1 20. POORLY-DIFFERENTIATED SCC 0 21. POORLY-DIFFERENTIATED SCC 0 On the other hand, for cases of OSCC taken in different gradings, although the expression was seen in all the gradings, yet cases of well-differentiated SCC showed higher grading of average IHC score, in decreasing order for Moderately-differentiated SCC and least for Poorly-differentiated SCC. DISCUSSION The most common OPMDs will have an increased chance of malignant transformation. ( 12 ) Out of all, lichen planus has a low risk of overall malignant transformation with the annual rate of 0.28%. ( 13 ) OSMF has more rate of transformation as compared to lichen planus; an average has been calculated to be 5.2% with an annual growth calculated to be 0.98%. ( 14 ) Results on meta-analysis on oral epithelial dysplasia have discovered the odds of malignant transformation of moderate/severe dysplasia are much higher than mild dysplasia (OR 2.37 99% CI 1.47–3.79). (15) Similar conclusive results have been obtained by our study in which the expression of BRCA2 gene was seen in case of mild dysplasia, and was absent in cases of moderate/ severe dysplasia. Thereby, this concludes to the fact that different treatment modalities is the need of the hour for different grades, even though they have same dysplastic changes, but their rates of malignant transformation are different from each other. Same is the case with different grades of OSCC, the higher grades are not only associated with increased risk of distant metastasis, but also the anaplastic changes these cells occupy, results in inactivation of BRCA2 gene making it difficult to treat effectively, increasing patient’s mortality and morbidity. The advantages of this study are: This is one of the first few studies reported which combines both the cases of OPMDs as well as different grades of OSCC to see how the expression of tumour suppressor gene gets expressed and suppressed in case of uncontrolled cell proliferation. This reports to the fact that in mild cases of dysplasia, this gene was expressed, whereas suppression was present in all the cases not only associated with increased rates of malignant transformation, but also the cases of OSCC with increased anaplastic behaviour showed no expression of the suppressor gene. The shortcomings of this study are: As this study has only few number of cases involved in both the categories, therefore more number of cases would be required in future studies to support the present results. Also, the cases can be followed up prospectively so that this can add more precision and help in increasing the quality of life of patients better by providing a better understanding on the molecular mechanisms that are responsible for progression of cancer. CONCLUSION The genetics of both the OPMDs as well as the OSCC is need of the hour in order to understand the underlying pathogenesis so that better treatment outcomes can be predicted. Declarations CONFLICTS OF INTEREST : NONE SOURCES OF FUNDING : NOT APPLICABLE References Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007; 36:575–80. Reibel J, Gale N, Hille J, et al. Oral potentially malignant disorders and oral epithelial dysplasia. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PPJ, editors. WHO Classification of Head and Neck Tumours. 4th ed.Lyon, France: IARC; 2017. p. 112–5. Mello FW, Miguel AFP, Dutra KL, et al. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med. 2018;47(7):633-640. Villa A, Villa C, Abati S. Oral cancer and oral erythroplakia: an update and implication for clinicians. Aust Dent J. 2011;56 (3):253-256. Parakh MK, Ulaganambi S, Ashifa N, Premkumar R, Jain AL. Oral potentially malignant disorders: clinical diagnosis and current screening aids: a narrative review. Eur J Cancer Prev. 2019. Ranganathan K, Kavitha L. Oral epithelial dysplasia: classifications and clinical relevance in risk assessment of oral potentially malignant disorders. J Oral Maxillofac Pathol. 2019;23 (1):19-27. Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia—a systematic review and meta-analysis. Head Neck. 2009;31(12):1600-1609. Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer 2019, 144, 1941–1953. Wang, H., Liu, J., Li, J., Zang, D., Wang, X., Chen, Y., et al. (2020). Identification of Gene Modules and Hub Genes in Colon Adenocarcinoma Associated with Pathological Stage Based on WGCNA Analysis. Cancer Genet. 242,1-7. Rivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 tumour suppressor gene: Important milestones at the various steps of tumorigenesis. Genes Cancer 2011; 2:466‑74. Bondarenko A, Angrisani N, Meyer-Lindenberg A, Seitz JM, Waizy H, Reifenrath J. Magnesium-based bone implants: immunohistochemical analysis of peri-implant osteogenesis by evaluation of osteopontin and osteocalcin expression. J Biomed Mater Res A. 2014; 102:1449–1457. Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia—a systematic review and meta-analysis. Head Neck. 2009;31(12):1600-1609. Giuliani M, Troiano G, Cordaro M, et al. Rate of malignant transformation of oral lichen planus: a systematic review. Oral Dis. 2019;25(3):693-709. Kerr AR, Warnakulasuriya S, Mighell AJ, et al. A systematic review of medical interventions for oral submucous fibrosis and future research opportunities. Oral Dis. 2011;17(Suppl 1): 42-57. Additional Declarations There is NO Competing Interest. 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class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/sup\u003e 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. \u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e 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. \u003csup\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/sup\u003e 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. \u003csup\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/sup\u003e 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.\u003c/p\u003e \u003cp\u003eIn 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. \u003csup\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/sup\u003e WHO has classified them on the basis of severity of derangement into Mild, Moderate and severe dysplasia. \u003csup\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/sup\u003e 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. \u003csup\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHead 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. \u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e Carcinogenesis is a multi-step, multi-gene, and multi-stage complex process involving the oncogene activation and inactivation of tumour suppressor genes. \u003csup\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/sup\u003e 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\u0026rsquo;s life outcomes.\u003c/p\u003e \u003cp\u003eTumour 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. \u003csup\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/sup\u003e 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\u0026ndash;\u003c/p\u003e \u003cp\u003e13 (Wooster \u003cem\u003eet al\u003c/em\u003e., 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.\u003c/p\u003e \u003cp\u003eTherefore, 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.\u003c/p\u003e"},{"header":"MATERIAL AND METHOD","content":"\u003cp\u003e2.1 Tissue samples\u003c/p\u003e\n\u003cp\u003eThe data of the diagnosed cases of both OPMDs as well as cases of OSCC in different grading stages were obtained from the archives. The diagnosis was reviewed and confirmed by two oral pathologists after retrieving the histopathological slides from the archives. Their respective formalin-fixed, paraffin-embedded (FFPE) samples were obtained from the archives of the Department and were then sent for immune-histochemical analysis. The tissue retrieval from the archives along with the information was obtained following the guidelines and approval from the institution. All the procedures have been performed following standard protocols.\u003c/p\u003e\n\u003cp\u003e2.2. Immunohistochemical Procedure\u003c/p\u003e\n\u003cp\u003eAll immunohistochemical stains were performed on tissue sections (4 micrometre thickness) prepared from formalin-fixed (4% neutral buffered formalin) paraffin-embedded tissue blocks. The sections were de-paraffinized in xylene and rehydrated through a series of graded alcohols. The endogenous peroxidase activity was blocked for 30 minutes in a solution containing 0.3% hydrogen peroxide. Antigen retrieval was performed using pressure method by putting the slides for 30 minutes. After antigen retrieval, the specimens were allowed to cool for 30 minutes and were then incubated at 4\u0026ordm;C overnight with the indicated primary antibodies. The diluted and used indicated antibodies were: BRCA2 (1:100, clone MS-13, Abcam, Cambridge, USA). After an overnight incubation with the primary antibody, the slides were incubated with post-primary solution for 30 minutes and were then incubated with the polymer for 30 minutes. The reactions were developed with diaminobenzidine (DAB), followed by Mayer\u0026rsquo;s haematoxylin counterstaining. The slides were then dehydrated in a graded series of ethanol and mounted using mountant which were then ready to be observed under microscope. The positive control to compare the staining of the tissues was that of breast cancer. All immunohistochemistry evaluation and analysis were carried out blinded to the patients\u0026rsquo; clinical outcomes.\u003c/p\u003e\n\u003cp\u003eAll the stained slides were then scanned using Zeiss Penta head and then the identification of the positive staining reaction was visualised as brown colour inside the nucleus which was identified and confirmed by two separate pathologists. Faint diffuse staining, isolated nuclear staining, weak staining of single interspersed cells or noise noted were scored negative and these cells were kept out of the annotation area. Next, to quantify and provide a mean expression percentage and a specific score for every case, the MagCam was attached to the microscope and QuPath-0.5.1 software was used for annotating the positive-stained cells and the expression percentage was taken for each case. The mean was taken after analysing the annotations from five separate High Power Fields (HPF).\u003c/p\u003e\n\u003cp\u003e2.3. Statistical Analysis\u003c/p\u003e\n\u003cp\u003eFor the statistical analysis, all acquired results were documented and evaluated using Microsoft excel. The mean expression percentage was calculated using SPSS software version 20.0.0. and then the IHC score was provided as per the scoring given by Bondarenko et al.\u003csup\u003e11\u003c/sup\u003e To prevent interpreting errors, the IHC slides were assessed by two reviewers who were blinded to the diagnostic data obtained from the archives.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eImmunohistochemical Findings\u003c/p\u003e\u003cp\u003eMean expression percentage and the respective IHC scores are documented for each case of OSCC and OPMD and are collectively presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e in separate sub-tables. For cases of potentially malignant disorders taken into account, only cases of mild dysplasia has shown positive expression in nucleus in lower one-third of the epithelium, whilst rest of the cases did not show any expression.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eREPRESENTING AVERAGE IHC SCORES IN CASES OF ORAL POTENTIALLY MALIGNANT DISORDERS FOR EXPRESSION OF BRCA2 GENE\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eS.NO.\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDIAGNOSIS\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eIHC SCORE (AVERAGE)\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMILD DYSPLASIA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMILD DYSPLASIA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMILD DYSPLASIA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATE DYSPLASIA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSEVERE DYSPLASIA\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLICHEN PLANUS\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLICHEN PLANUS\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLICHEN PLANUS\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eORAL SUBMUCOUS FIBROSIS\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eREPRESENTING AVERAGE IHC SCORES IN CASES OF ORAL SQUAMOUS CELL CARCINOMA FOR EXPRESSION OF BRCA2 GENE\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eS.NO.\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDIAGNOSIS\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eIHC SCORE (AVERAGE)\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWELL-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWELL-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWELL-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWELL-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWELL-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMODERATELY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePOORLY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePOORLY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePOORLY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePOORLY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePOORLY-DIFFERENTIATED SCC\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eOn the other hand, for cases of OSCC taken in different gradings, although the expression was seen in all the gradings, yet cases of well-differentiated SCC showed higher grading of average IHC score, in decreasing order for Moderately-differentiated SCC and least for Poorly-differentiated SCC.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe most common OPMDs will have an increased chance of malignant transformation. \u003csup\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/sup\u003e Out of all, lichen planus has a low risk of overall malignant transformation with the annual rate of 0.28%. \u003csup\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/sup\u003e OSMF has more rate of transformation as compared to lichen planus; an average has been calculated to be 5.2% with an annual growth calculated to be 0.98%. \u003csup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/sup\u003e Results on meta-analysis on oral epithelial dysplasia have discovered the odds of malignant transformation of moderate/severe dysplasia are much higher than mild dysplasia (OR 2.37 99% CI 1.47\u0026ndash;3.79). \u003csup\u003e(15)\u003c/sup\u003e Similar conclusive results have been obtained by our study in which the expression of BRCA2 gene was seen in case of mild dysplasia, and was absent in cases of moderate/ severe dysplasia. Thereby, this concludes to the fact that different treatment modalities is the need of the hour for different grades, even though they have same dysplastic changes, but their rates of malignant transformation are different from each other.\u003c/p\u003e \u003cp\u003eSame is the case with different grades of OSCC, the higher grades are not only associated with increased risk of distant metastasis, but also the anaplastic changes these cells occupy, results in inactivation of BRCA2 gene making it difficult to treat effectively, increasing patient\u0026rsquo;s mortality and morbidity.\u003c/p\u003e \u003cp\u003eThe advantages of this study are: This is one of the first few studies reported which combines both the cases of OPMDs as well as different grades of OSCC to see how the expression of tumour suppressor gene gets expressed and suppressed in case of uncontrolled cell proliferation. This reports to the fact that in mild cases of dysplasia, this gene was expressed, whereas suppression was present in all the cases not only associated with increased rates of malignant transformation, but also the cases of OSCC with increased anaplastic behaviour showed no expression of the suppressor gene.\u003c/p\u003e \u003cp\u003eThe shortcomings of this study are: As this study has only few number of cases involved in both the categories, therefore more number of cases would be required in future studies to support the present results. Also, the cases can be followed up prospectively so that this can add more precision and help in increasing the quality of life of patients better by providing a better understanding on the molecular mechanisms that are responsible for progression of cancer.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe genetics of both the OPMDs as well as the OSCC is need of the hour in order to understand the underlying pathogenesis so that better treatment outcomes can be predicted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eCONFLICTS OF INTEREST\u003c/u\u003e: NONE\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eSOURCES OF FUNDING\u003c/u\u003e: NOT APPLICABLE\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWarnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. \u003cem\u003eJ Oral Pathol Med\u003c/em\u003e 2007; 36:575\u0026ndash;80.\u003c/li\u003e\n \u003cli\u003eReibel J, Gale N, Hille J, et al. Oral potentially malignant disorders and oral epithelial dysplasia. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PPJ, editors. WHO Classification of Head and Neck Tumours. 4th ed.Lyon, France: IARC; \u0026nbsp;2017. p. 112\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eMello FW, Miguel AFP, Dutra KL, et al. Prevalence of oral potentially malignant disorders: a systematic review and meta-analysis. J Oral Pathol Med. 2018;47(7):633-640.\u003c/li\u003e\n \u003cli\u003eVilla A, Villa C, Abati S. Oral cancer and oral erythroplakia: an update and implication for clinicians. Aust Dent J. 2011;56 (3):253-256.\u003c/li\u003e\n \u003cli\u003eParakh MK, Ulaganambi S, Ashifa N, Premkumar R, Jain AL. Oral potentially malignant disorders: clinical diagnosis and current screening aids: a narrative review. Eur J Cancer Prev. 2019.\u003c/li\u003e\n \u003cli\u003eRanganathan K, Kavitha L. Oral epithelial dysplasia: classifications and clinical relevance in risk assessment of oral potentially malignant disorders. J Oral Maxillofac Pathol. 2019;23 (1):19-27.\u003c/li\u003e\n \u003cli\u003eMehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia\u0026mdash;a systematic review and meta-analysis. Head Neck. 2009;31(12):1600-1609.\u003c/li\u003e\n \u003cli\u003eFerlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Pi\u0026ntilde;eros, M.; Znaor, A.; Bray, F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. \u003cem\u003eInt. J. Cancer\u003c/em\u003e 2019, 144, 1941\u0026ndash;1953.\u003c/li\u003e\n \u003cli\u003eWang, H., Liu, J., Li, J., Zang, D., Wang, X., Chen, Y., et al. (2020). Identification of Gene Modules and Hub Genes in Colon Adenocarcinoma Associated with Pathological Stage Based on WGCNA Analysis. \u003cem\u003eCancer Genet.\u003c/em\u003e 242,1-7.\u003c/li\u003e\n \u003cli\u003eRivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 tumour suppressor gene: Important milestones at the various steps of tumorigenesis. Genes Cancer 2011; 2:466‑74.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Bondarenko A, Angrisani N, Meyer-Lindenberg A, Seitz JM, Waizy H, Reifenrath J. Magnesium-based bone implants: immunohistochemical analysis of peri-implant osteogenesis by evaluation of osteopontin and osteocalcin expression.\u0026nbsp;\u003cem\u003eJ Biomed Mater Res A.\u0026nbsp;\u003c/em\u003e2014;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e102:1449\u0026ndash;1457.\u003c/li\u003e\n \u003cli\u003eMehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia\u0026mdash;a systematic review and meta-analysis. Head Neck. 2009;31(12):1600-1609.\u003c/li\u003e\n \u003cli\u003eGiuliani M, Troiano G, Cordaro M, et al. Rate of malignant transformation of oral lichen planus: a systematic review. Oral Dis. 2019;25(3):693-709.\u003c/li\u003e\n \u003cli\u003eKerr AR, Warnakulasuriya S, Mighell AJ, et al. A systematic review of medical interventions for oral submucous fibrosis and future research opportunities. Oral Dis. 2011;17(Suppl 1): 42-57.\u003cu\u003e\u003c/u\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"OSCC, OPMD TSG, BRCA2 gene.","lastPublishedDoi":"10.21203/rs.3.rs-4733804/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4733804/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eOral Potentially Malignant Disorders (OPMD) are 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). Once diagnosed, they pose challenge because of the intrinsic potential to develop into OSCC. 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. Carcinogenesis is a multi-step, multi-gene, and multi-stage complex process involving the oncogene activation and inactivation of tumour suppressor genes. Thereby, not only knowing 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\u0026rsquo;s life outcomes. Thereby, this study identified the expression of tumour suppression gene (TSG), BRAC2 gene, in cases of both OSCC and OPMDs. The results showed that with increased grade and severity of the lesion, the expression of this gene was not seen in either category of the lesions. Thereby, we conclude that a large no of sample size study would be the need to confirm the findings.\u003c/p\u003e","manuscriptTitle":"Profiling Expression of Brac2 Gene in Cases of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders-a Pilot Study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 12:49:07","doi":"10.21203/rs.3.rs-4733804/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9160b629-1c3e-4ea9-95bd-f802ac5fdc9b","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":35804568,"name":"Health sciences/Biomarkers"},{"id":35804569,"name":"Biological sciences/Cell biology"}],"tags":[],"updatedAt":"2024-08-09T12:49:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-09 12:49:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4733804","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4733804","identity":"rs-4733804","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}