Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Supervisor

Darling, Mark

Abstract

Oral Lichen Planus (OLP) is a potentially malignant disorder that has a malignant transformation rate of approximately 1%. Current management includes incisional biopsy and grading of dysplasia, if present. This may not be a reliable predictive tool for malignant transformation. Tissue biomarkers such as S100A7 may provide a more accurate method of risk determination. The proposed mechanism is an association between S100A7 and the MAPK signalling pathway. Paraffin embedded sections of OLP that progressed and did not progress on serial biopsy were selected. The tissues were stained via S100A7 immunohistochemistry. S100A7 was quantified using an Immunoreactivity score, QuPath and StraticyteÔ. Phosphorylated MAPK proteins and WNT proteins were also evaluated. Based on Pearson correlation coefficients, the Immunoreactivity score correlated well with both StraticyteÔ and Qupath scores. The 3 predictive scores can distinguish Lichen Planus from Normal tissue based on quantification of S100A7, however, S100A7 cannot predict which Lichen Planus lesion might progress to malignancy. Furthermore, the pathway involved in progression of this inflammatory lesion also remains uncertain. Biomarker S100A7 does not aid in the accurate prediction of transformation in Lichen Planus and hence should not be used to guide clinical management.

Keywords: Potentially malignant disorder, Lichen planus, Dysplasia.

Summary for Lay Audience

Oral Lichen Planus is a relatively common disorder of the oral cavity with a small risk of turning into cancer. It is difficult to predict which individuals living with this disorder will develop cancer. S100A7 is a cellular protein that has been found to be present in increased amount in certain cancers including those of the head and neck. We attempted to show that S100A7 would be elevated in the Oral Lichen Planus lesions that eventually turned into precancerous and cancerous tissue. We used an antibody that attaches to S100A7 protein and measured the amount of S100A7 using three different methods. We compared the amount of S100A7 in Oral lichen planus that was known to progress to cancer, precancerous tissue, and stay the same on repeat biopsy. For comparison, we also contrasted the above tissues with S100A7 in normal tissue, inflamed tissue and healing tissue.

To determine how S100A7 may be involved with progression to precancer/cancer, we examined for a possible relationship with the Mitogen activated Protein Kinase (MAPK) system along with Beta-Catenin and Cyclin D1. These are two different cellular protein signaling mechanisms that have been shown to be involved with key steps in the development of cancer.

Our results show that S100A7 was elevated in Oral Lichen Planus and other inflamed tissues when compared to normal tissue; however, it could not be used to accurately predict precancerous and cancerous transformation. The cellular pathways involved in the transformation process need to be better elucidated. This will likely aid in selection of biomarker(s) to predict this rare event. Epithelial to Mesenchymal transition through E-Cadherin and Beta-Catenin may be worth looking further into. In summary, S100A7 should not be used to guide clinical management of Lichen Planus. Studies to confirm or refute our results as well as investigating other potential biomarker are required if biomarkers are to be used to guide management in these lesions.

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