Immunophenotypic Characterization of Tumor-Associated Macrophages in Oral Carcinogenesis: An Observational Study

Tumor-associated macrophages are key components of the tumor microenvironment in oral carcinogenesis; however, their role is not yet fully understood. We aimed to characterize the expression of macrophage (M) markers across the spectrum of oral carcinogenesis, including oral leukoplakias (OL) and oral squamous cell carcinomas (OSCCs). This immunohistochemical study analyzed the macrophage density (cells/mm2) based on the expression of CD68 (pan-macrophage), CD163 (M2), and CD80 (M1) in 81 samples, including healthy mucosa (n = 16), OL (n = 30), and OSCC (n = 35), in both epithelial and subepithelial compartments. All markers showed a progressive increase across the study groups, with significantly higher densities in OSCC than in healthy mucosa (p < 0.001), consistently higher in the subepithelial compartment. CD163 was the most expressed marker (increasing from 78.96 cells/mm2 in healthy mucosa to 300.56 cells/mm2 in OSCC), whereas CD80 was the least abundant, particularly in OSCC (35.66 cells/mm2 in healthy tissue to 188.49 cells/mm2 in OSCC). No significant associations were observed between biomarker expression and clinicopathological variables. These results support the involvement of macrophages during oral carcinogenesis, particularly CD163+ (M2) cells, and highlight the potential prognostic and therapeutic relevance of these markers.