IMMUNOHISTOCHEMICAL EVALUATION OF YAP, TEAD, MMP-7, AND MMP-9 IN GIANT CELL LESIONS
Giant Cell Tumors; Giant Cell Granuloma; Hippo Signaling Pathway; Matrix Metalloproteinases.
Giant cell lesions (GCLs) comprise a heterogeneous group of lesions characterized by the presence of osteoclast-like multinucleated giant cells (MGCs) and variable clinical behavior. Among them, Central Giant Cell Lesion (CGCL) of the jaws and Giant Cell Tumor of Bone (GCTB) of the long bones are the most representative entities. Elucidating the molecular mechanisms underlying the biological behavior of these lesions is essential for understanding their pathogenesis. In this context, the Hippo pathway, particularly the YAP1/TEAD1 axis, has emerged as a key regulator of cell proliferation, differentiation, and extracellular matrix (ECM) remodeling, processes in which matrix metalloproteinases (MMP-7 and MMP-9) also play important roles. Therefore, this study evaluated the immunoexpression of YAP1, TEAD1, MMP-7, and MMP-9 in CGCLs and GCTBs. The sample consisted of 31 CGCL cases (17 aggressive and 14 non-aggressive), 17 GCTBs, and 7 osteosarcomas (OS) included as a comparative group with greater biological aggressiveness. Immunohistochemical analysis was performed semiquantitatively for YAP1, TEAD1, and MMP-7, whereas MMP-9 expression was evaluated descriptively. Statistical analyses included the Kruskal-Wallis test followed by Dunn's post hoc test, the Mann-Whitney test, and Spearman's correlation analysis, adopting a significance level of 5%. The results demonstrated a predominance of YAP1 score 1 in CGCLs (61.2%) and score 3 in all OS cases (100%), with significant differences between non-aggressive CGCLs and OS (p = 0.006) and between aggressive CGCLs and OS (p = 0.022). TEAD1 expression was heterogeneous, with no significant differences among the groups (p = 0.097). MMP-7 exhibited higher immunostaining scores in non-aggressive CGCLs than in GCTBs (p = 0.048), with a predominance of score 3 in this subgroup (71.4%). MMP-9 showed intense and diffuse immunostaining in the multinucleated giant cells of both CGCLs and GCTBs, whereas OS displayed a predominantly nuclear staining pattern with focal cytoplasmic positivity. No significant associations were observed between marker expression and the clinicoradiographic characteristics of CGCLs (p > 0.05). Correlation analysis demonstrated a positive association between YAP1 and TEAD1 in the overall sample (r = 0.553; p < 0.001) and in GCTBs (r = 1.000; p < 0.001), with no significant correlation between YAP1 and MMP-7. These findings suggest that the association between nuclear YAP1 and the immunoexpression of the transcription factor TEAD1 indicates that Hippo pathway activation may influence the biological behavior of GCLs.