Immunohistochemical expression of smoothened in periocular basal cell, squamous cell and sebaceous carcinomas

Inhibition of Smoothened (SMO), a key protein in the Hedgehog signaling pathway, is effective for locally advanced basal cell carcinoma (BCC), but is not yet used for sebaceous carcinoma (SEB) or squamous cell carcinoma (SCC). This study quantified SMO expression and its relationship to proliferative activity in non-nodular periocular BCC, SEB and SCC. Tumor samples from 47 patients (17 BCC, 15 SCC, and 15 SEB) were immunostained and analyzed digitally to assess SMO optical density and Ki67 hot-spot index. SMO expression was significantly higher in all tumor types than in surrounding stroma, with no inter-tumor differences. SMO correlated with mitotic count in BCC but not in SCC or SEB, whereas higher SMO consistently paralleled a higher Ki67 index across all three carcinomas. These findings indicate that SMO expression and proliferative activity are closely linked and suggest that Hedgehog inhibitors, proven in BCC, warrant clinical evaluation as adjuvant or neoadjuvant therapy for periocular SEB and SCC.