Electronic Thesis and Dissertation Repository

Thesis Format

Alternative Format

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Supervisor

Darling, Mark

2nd Supervisor

Olea-Popelka, Francisco

Co-Supervisor

Abstract

Oral potentially malignant disorders (OPMDs) represent a diverse array of conditions with an elevated propensity for progressing into oral squamous cell carcinoma (OSCC). My study aims to enhance the early detection of OPMDs by investigating the expression levels of specific biomarkers, their correlation with disease severity, and the concordance between clinical and pathological diagnoses. Using nanoString gene expression analysis and immunohistochemical (IHC) staining, I identified significantly elevated levels of S100A7, Ki67, and Vimentin in OPMD tissues compared to normal controls, suggesting their potential as biomarkers for early detection and monitoring of disease progression. Conversely, E-cadherin showed reduced expression in OPMDs, indicating disruptions in cellular adhesion and the MAPK signaling pathway. My findings on moderate concordance between clinical and histopathological diagnoses, highlighting the complexity of diagnosing OPMDs based solely on clinical oral examination and the importance of histopathological confirmation. This underscores the need for improved diagnostic accuracy through enhanced clinical training and the use of molecular diagnostic tools. Despite limitations such as small sample size and geographic constraints, my research underscores the critical role of integrating molecular data with clinical diagnostics to improve the early detection and risk stratification of OPMDs. Future research should focus on developing comprehensive predictive models by integrating multiple biomarkers and leveraging digital pathology and artificial intelligence to refine these models. This approach holds promise for early intervention and better management of patients at risk of malignant transformation, ultimately enhancing patient care and outcomes.

Summary for Lay Audience

In my study, I explored how molecular methods can help identify early signs of disease in certain oral lesions known as oral potentially malignant disorders (OPMDs). These disorders, which include various conditions in the mouth, have a higher risk of developing into a serious form of oral cancer called oral squamous cell carcinoma (OSCC). Early detection of these conditions is crucial, as they have a higher likelihood to become cancerous. To achieve this, I collected biopsy samples from patients diagnosed with OPMDs and analyzed the genetic material (RNA) extracted from these samples. I also used a technique called Immunohistochemistry (IHC) to visualize specific proteins within the cells, which could indicate the disease's progression. My study found that a protein called S100A7 was present in higher amounts in the precancerous tissues compared to normal mouth tissue. The levels of S100A7 were also higher in more severe cases, suggesting it could be used to identify early cancer risk. Additionally, proteins called Ki67 and Vimentin were also higher in OPMD tissues, which are linked to cell growth and inflammation. On the other hand, proteins called E-cadherin was lower in OPMD patient group, indicating problems with cell connections and signaling. The study also highlighted the importance of combining clinical diagnoses with molecular analysis to improve the accuracy of detecting OPMDs. While clinical examinations are important, the integration of molecular data can provide a deeper understanding of the disease and help identify high-risk patients. I believe this approach could lead to early detection and intervention of OPMDs, and better care for patients.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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