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Molecular Grading of Oral Squamous Cell Carcinomas Infected with EBV
1Departement of Oral Pathology and Maxillofacial, Faculty of Dental Medicine, Universitas Airlangga, Mayjen. Prof. Dr. Moestopo 47, Surabaya, Indonesia.
Abstract:
Background: Squamous Cell Carcinoma (SCC) is a type of cancer that is often found in oral cavity and areas of the head and neck. Viruses are major etiological factors through production of factors that can disturb proliferation and apoptosis regulators such as p53i, c-myc and bcl-2. This study aimed to determine the molecular grading of oral squamous cell carcinoma (OSCCs) infected with the Epstein-Barr Virus (EBV). Methods: Twenty-seven OSCC patients underwent biopsy to detect EBV infection through in situ hybridization for RNA EBV (EBER) and immunohistochemical analysis of latent membrane protein-1 (LMP-1) and EBV nuclear antigen-1 (EBNA-1). To assess molecular grades, cell proliferation and apoptosis regulator expression i.e. inactive p53 (p53i), c-myc and bcl-2, were immunohistochemically analysed. Results: The cases were divided into two groups; infected and non-infected by EBV. Regression analysis showed that only EBNA-1 expression could affect p53i expression. Based on regression equations molecular grading of OSCCs infected by EBV was divided into three: Grade I (low), EBNA-1 expression was 7.60, and p53i expression was 9.74-17.5; Grade II (medium), EBNA-1 expression was 7.61-19.7, and p53i 17.5-30.1; Grade III (high), EBNA-1 expression was 19.71, and p53i ≥ 30.1. Conclusion: In OSCC infected with EBV, only EBNA-1 expression can influence p53i expression
Insights
Epstein-Barr Virus (EBV) infection in oral squamous cell carcinoma (OSCC) influences molecular grading. Only EBV nuclear antigen-1 (EBNA-1) expression impacts inactive p53 (p53i) levels, establishing a new grading system for EBV-positive OSCC.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Squamous Cell Carcinoma (SCC) is a prevalent cancer in the head and neck, with viruses being key etiological factors.
- Viral infections can disrupt cellular proliferation and apoptosis regulators like p53, c-myc, and bcl-2.
Purpose of the Study:
- To determine the molecular grading of oral squamous cell carcinoma (OSCC) in patients infected with the Epstein-Barr Virus (EBV).
- To investigate the relationship between EBV infection and the expression of proliferation and apoptosis regulators.
Main Methods:
- Biopsies from 27 OSCC patients were analyzed for EBV infection using in situ hybridization (EBER) and immunohistochemistry (LMP-1, EBNA-1).
- Cell proliferation and apoptosis regulator expression (p53i, c-myc, bcl-2) were assessed via immunohistochemical analysis to establish molecular grades.
Main Results:
- The study identified a correlation where only EBV nuclear antigen-1 (EBNA-1) expression significantly affected inactive p53 (p53i) expression.
- A novel molecular grading system for EBV-infected OSCC was proposed, categorizing cases into Grade I (low), Grade II (medium), and Grade III (high) based on EBNA-1 and p53i expression levels.
Conclusions:
- In EBV-infected OSCC, EBNA-1 expression is the sole determinant influencing p53i expression.
- This finding suggests a specific molecular pathway in EBV-associated oral cancers that can be utilized for refined grading and potentially targeted therapies.
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