ADP-Ribosylation Factor-Like Protein 4C (ARL4C) as a Marker for Prediction of Recurrence in Ameloblastoma

Introduction and Aims Ameloblastoma is a benign epithelial neoplasm with a significant recurrence rate. Despite advancements in surgical techniques, accurately predicting recurrence remains a considerable challenge. ADP-ribosylation factor-like protein 4C (ARL4C) is implicated in ameloblastoma and has been associated with shorter recurrence-free survival (RFS) in multiple malignancies. This study aimed to investigate the role of ARL4C in predicting the recurrence of ameloblastoma. Methods This retrospective study consisted of 34 conventional ameloblastomas with no recurrence (AMNRs), 20 primary tumours of ameloblastoma with known recurrence (PAMRs), and 20 recurrent ameloblastomas (RAMs) from the same patient as the PAMR group. Recurrent cases were defined as tumour reappearance >1 year after primary treatment. All samples were immunohistochemically examined for ARL4C expression and evaluated using the immunoreactive scoring (IRS) method. The Mann-Whitney and Wilcoxon signed-rank tests were used to compare ARL4C expression between groups. Cox proportional hazards models were performed to identify independent predictors of recurrence. Kaplan-Meier analysis was applied to analyse RFS based on the optimal IRS cutoff value obtained from receiver operating characteristic analysis. Results ARL4C expression was observed in 88% of AMNR cases and 100% of PAMR and RAM cases. ARL4C expression was significantly higher in PAMR compared to AMNR ( P < .001), while no difference was observed between paired PAMR and RAM samples. Multivariate Cox analysis identified higher ARL4C expression and conservative treatment as independent risk predictors of recurrence ( P < .05). IRS ≥9 was significantly associated with shorter RFS ( P < .001). Conclusion ARL4C expression represents a potential predictive marker for ameloblastoma recurrence, with possible utility in risk stratification and individualised treatment planning. However, these findings remain tentative, pending validation in independent cohorts. Clinical Relevance ARL4C expression has the potential to predict recurrence risk in ameloblastoma and inform treatment planning, facilitating more tailored decisions regarding conservative or radical management.