Immunohistochemical Study of GATA3, c-KIT/CD117, CD56 and CD45 Expression in Proliferative Verrucous Leukoplakia (PVL), PVL-Associated Oral Squamous Cell Carcinoma and Oral Leukoplakia

<b>Background/Objectives</b>: Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder characterized by a high risk for cancer development. Current evidence suggests that the evolution and malignant transformation of PVL is driven by a reciprocal crosstalk between the epithelial cells and the subepithelial immune microenvironment. The aim of the present study was to compare for the first time the immunohistochemical expression of the immune response-related proteins GATA-binding protein 3 (GATA3), c-KIT/cluster of differentiation (CD)117, CD56 and CD45 between PVL, PVL-associated oral squamous cell carcinoma (OSCC) and solitary (localized) oral leukoplakia (OL) cases. <b>Methods</b>: Thirty-six formalin-fixed and paraffin-embedded tissue specimens were used; sixteen from 8 patients with PVL, ten from 10 patients with PVL-OSCC and ten from 10 patients with OL. Immunohistochemistry was conducted using monoclonal primary antibodies against GATA3, c-KIT/CD117, CD56 and CD45. A semi-quantitative method was applied to score staining, and statistical analysis included Wilcoxon signed-rank test, Kruskal-Wallis test with Dunn's post hoc test and Spearman's correlation coefficient test. <b>Results</b>: A significantly decreased GATA3 expression was found in PVL-OSCC cases compared with PVL and OL cases. c-KIT/CD117 and CD56 proteins were consistently expressed in all study groups, while a significantly higher CD45 expression was noted in PVL than OL. No significant correlation between markers was found. <b>Conclusions</b>: These data collectively underscore an activated yet disturbed immune response that might be involved in the development and progression of malignancy in PVL that may also be considered as unique and interesting in vivo model of oral carcinogenesis.