Oral Epithelial Remodeling Associated with Long-Term Dental Amalgam Contact: A Histopathological and Immunohistochemical Study

Prolonged contact between oral mucosa and dental amalgam restorations may influence local epithelial homeostasis, although the immunohistochemical profile of clinically non-dysplastic mucosa exposed to long-term restorative materials remains insufficiently defined. This study investigated histopathological remodeling and the expression patterns of cytokeratin 19 (CK19), Ki67, and p53 in oral mucosal specimens adjacent to long-standing amalgam restorations. A total of 108 specimens were retrospectively analyzed, including 78 samples from mucosa in direct contact with amalgam restorations and 30 control specimens without amalgam exposure. Exposed cases were categorized according to contact duration: 5–10 years, 11–20 years, and ≥21 years. Epithelial and stromal changes were semi-quantitatively assessed, and immunohistochemical staining was evaluated using predefined scoring criteria. An exploratory Integrated Epithelial Remodeling Score (IERS), combining basal hyperplasia, inflammatory infiltrate, CK19 distribution, and Ki67 proliferative index, was used to estimate cumulative remodeling intensity. Longer amalgam exposure was significantly associated with increased inflammatory infiltrate, basal epithelial expansion, suprabasal CK19 expression, and higher Ki67 labeling indices (all p < 0.001). CK19 redistribution showed positive associations with both inflammatory intensity and epithelial proliferative activity. IERS values differed significantly among exposure groups (p < 0.001), with more pronounced remodeling in intermediate- and long-duration exposure categories. p53 expression showed statistically detectable but heterogeneous variation. No epithelial dysplasia was observed. These findings suggest that long-term contact with dental amalgam restorations is associated with a coordinated, non-dysplastic remodeling phenotype of the oral mucosa, characterized by inflammatory activation, CK19 redistribution, and reactive proliferative reinforcement. In this context, suprabasal CK19 expression may reflect adaptive epithelial plasticity rather than preneoplastic transformation.