HuR-ΔNp63 Regulation and E-Cadherin Expression in Tumor Budding and Bone Remodeling of Ameloblastoma.

Ameloblastoma is a benign odontogenic tumor characterized by locally infiltrative growth and a high recurrence rate despite minimal cytological atypia. Histologically, tumor budding-small epithelial projections arising from tumor nests-is frequently observed and has been suggested to be associated with recurrence; however, its molecular basis and pathological significance remain unclear. This study aimed to clarify the molecular characteristics of tumor budding, its relationship with surrounding bone remodeling, and its possible contribution to tumor recurrence. Immunohistochemical analyses revealed that HuR and ΔNp63 were co-expressed in budding areas of ameloblastoma. In vitro experiments using the AM-1 ameloblastoma cell line demonstrated that HuR binds to ΔNp63 mRNA and stabilizes its expression. Genetic knockout of ΔNp63 increased E-cadherin expression, consistent with the reduced E-cadherin expression observed immunohistochemically in ΔNp63-positive budding areas. Histological examination of serial sections revealed bone remodeling at the tumor front, with newly formed bone surrounding tumor nests together with areas of bone resorption. These findings suggest that alterations in HuR, ΔNp63, and E-cadherin are associated with tumor budding and reduced epithelial cell-cell adhesion. Accompanying bone remodeling may complicate tumor removal and contribute to recurrence.