Diversity of Molecular Interaction in the Immune Microenvironment and Exosome-Rich Compartments of Oral Leukoplakia Before Its Transformation into Carcinoma

Although oral leukoplakia (OL) is recognized as a precancerous lesion, only a proportion of cases undergo malignant transformation (7,2 % to 9.5%). That's why recently, increasing attention has been directed toward molecular biomarkers that may better reflect the biological behaviour of OL Infiltration density of T and B lymphocytes, macrophages, plasma cells were assessed semi-quantitatively using a 4-point scale adapted from Nankivel study. CD9 antigen was assessed in epithelial and immune cells by counting them in three 400x fields. CD138 and CD68 biomarkers were associated with significantly elevated expression across both clinical types of OL where dysplasia was diagnosed. The increase in infiltration density with CD3 and CD20 labelled lymphocytes was statistically reliably confirmed only in non-homogeneous OL with dysplasia. CD9, as a protein reflecting the exosome compartments, revealed the interaction between the epithelium and immune cells. A moderate, statistically significant positive correlation was found only in leukoplakia with dysplasia between CD9+ immune cell levels and the number of epithelial layers expressing this antigen. Assessment of combinations of CD3, CD9, CD20, CD68, and CD138 biomarker expression, cons idering clinical type of leukoplakia, particularly non-homogeneous, appears to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia.