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Lin, Iris

University of British Columbia

Cancer is known as the “wound that never heals,” in reference to its capacity to dysregulate the inflammatory process to facilitate tumour growth and invasion. While these mechanisms have been extensively studied across various cancer types, the role of inflammation in oral potentially malignant disorders (OPMD) remains largely understudied. The overarching objective of this work was to explore whether chronic inflammation influences the clinical and histological behaviour of OPMD. To this end, we first conducted a clinicopathological analysis of lichenoid mucositis with dysplasia (LMD), to assess whether the histological features seen in these lesions are indicative of malignant risk or a reactive byproduct of intense inflammation. We found that the dysplasia seen in these lesions are still apt to progress, and warrant clinical monitoring. The oral cavity, being accessible to routine screening, presents a unique opportunity for the early detection and prevention of cancer; this project uncovered certain clinical features that were associated with risk and which may aid in diagnosis, early detection, and clinical management. To further understand the biology of these lesions, we optimized a multiplexed staining protocol coupled with a machine-based digital pathology platform to quantify key antitumourigenic and pro-tumourigenic immune cells in dysplasia with and without lichenoid inflammation, before testing the association of these cells with malignant progression. We found that LMD presented with immune cell patterns characteristic of oral lichen planus (OLP), providing some insight into the pathogenesis of a disease group that has been subject to heavy debate. Irrespective of lichenoid features, we found activation of both anti- and pro-tumourigenic immune cell populations in low-grade dysplasia, in line with the immunoediting theory. Progressing cases showed a greater proportion of CD163+ and CD8+FOXP3+ cells, and a lesser proportion of CD8+ cells, indicating that the characterization of immune cells in OPMD may be promising avenues of biomarker research. This work advances novel visualization techniques to profile OPMD and addresses existing uncertainties regarding inflammation in oral premalignancy. Further exploration of this field may provide insight to front-line clinicians and pathologists in clinical decision-making and lays out groundwork for future biomarker and risk prediction research.

Text

2024-10-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89473

Craniofacial Science

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/