Programmed cell death ligand 1 in correlation with BRAFV600E mutation, molecular characteristics and biological behavior in ameloblastoma.
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OBJECTIVE: To investigate the expression of Programmed cell death ligand 1 (PD-L1) in Ameloblastoma (AM) and its correlation with BRAFV600E mutation as well as the expression of Cytotoxic CD8+ T cells (CD8+ T) and Forkhead box protein 3 (FoxP3) in the immune microenvironment. And to preliminarily explore the potential association of PD-L1 with the biological behavior and Disease-free survival (DFS) of patients with AM, so as to provide a theoretical reference for clinical diagnosis and treatment. METHODS: Fifty formalin-fixed paraffin-embedded (FFPE) specimens of AM were enrolled in this study. Immunohistochemistry (IHC) was performed to detect the expression of BRAFV600E mutant protein, CD8+ T cells, FoxP3+ T cells and PD-L1. Molecular testing for the BRAFV600E mutation was further conducted in 29 eligible AM specimens. PD-L1 expression was evaluated by IHC, and the combined positive score (CPS) ≥ 1 was defined as PD-L1 positivity. The chi-square test and Fisher's exact test were used for bivariate statistical analysis. Survival analysis was performed using the Kaplan-Meier method with the log-rank test, and the Cox proportional hazards regression model was applied to identify predictive factors for DFS. RESULTS: Of the 50 patients, 42 (84%) were PD-L1 positive. Forty-one cases were BRAF mutation-positive, and 38 of them (92.68%) showed PD-L1 positivity, indicating a significant association between the two (p = 0.003). No significant correlations were found between PD-L1 and other major indicators, including CD8+ T cells (p = 0.247), FoxP3+ cells (p = 0.702), and pathological subtype (p = 0.667). In exploratory survival analysis, patients with high CD8+ T cell infiltration exhibited a tendency of prolonged DFS compared with those with low infiltration (HR = 0.112, 95%CI: 0.014-0.913, p = 0.041). CONCLUSION: PD-L1 expression is frequently observed in AM with BRAFV600E mutation, whereas no significant correlation is identified between PD-L1 and the clinicopathological parameters associated with AM. Within the limitation of relatively short follow-up duration, high CD8+T cell infiltration was indicated to be potentially correlated with favorable DFS in AM patients, which needs further verification in cohorts with longer follow-up.