Immunological Microenvironment Diversity in Homogeneous and Non-Homogeneous Oral Leukoplakia

Oral leukoplakia (OL) is a potentially malignant lesion, but only a proportion of cases undergo transformation to carcinoma (7.2% to 9.5%). The aim of this study was to analyze the possible differences and the role of immune cells in homogeneous and non-homogeneous OL at different grades of dysplasia. The infiltration density of T and B lymphocytes, macrophages, plasma cells, and cells expressing CD9 antigen was assessed semi-quantitatively in 50 OL cases using a 4-point scale-score 1 (<5%), score 2 (6-10%), score 3 (11-15%) and score 4 (16-20%)-via manual counting by two morphologists. Both clinical types of OL that showed dysplasia had noticeably higher proportions of CD138+ and CD68+ immune cells. Statistical analysis confirmed that only non-homogeneous OL with dysplasia showed an increase in the infiltration density of CD3+ and CD20+ lymphocytes. There was a statistically significant moderate positive correlation between the amount of CD9+ cells in the lamina propria and the number of labeled epithelial layers in OL of different thicknesses. Expression of CD138 and CD9 proteins in epithelial and connective tissue cells in OL indicates active epithelial-mesenchymal interaction during the premalignant stage of OL, but the expression of these markers in epithelial and immune cells was completely the opposite. The evaluation of CD3, CD20, CD9, CD138, and CD68 antigen expression, particularly in non-homogeneous leukoplakia, improves the accuracy of malignancy risk assessment in patients with dysplasia.