Expression of SHH Signaling Pathway Genes in Pleomorphic Adenoma and Mucoepidermoid Carcinoma: A Preliminary Study

Objective: Sonic hedgehog (SHH) signaling is a pivotal regulator of epithelial–mesenchymal interactions and oncogenesis, yet its regulatory dynamics in salivary gland tumors remain poorly defined. This study quantified the mRNA expression of key SHH pathway components—SHH, glioma-associated oncogene (GLI1), suppressor of fused (SUFU), hedgehog-interacting protein (HHIP), and signal transducer and activator of transcription 3 (STAT3)—to differentiate the molecular profiles of benign pleomorphic adenoma (PA) and malignant low-grade mucoepidermoid carcinoma (LG-MEC). Methods: In this cross-sectional molecular analysis, quantitative polymerase chain reaction (qPCR) was utilized to analyze 27 tissue samples categorized into: Normal salivary glands (NSG, n = 7), PA ( n = 9), and LG-MEC ( n = 11). Relative gene expression was calculated using the 2-ΔΔCt (cycle threshold [Ct]) method. Differences between groups were analyzed using the Kruskal–Wallis test with pairwise post-hoc comparisons. Results: A significant variation in the expression of SUFU, a key negative regulator of the SHH pathway, was observed across the groups ( p = .040). Pairwise analysis revealed a significant downregulation/alteration of SUFU in PA compared to NSG ( p = .035), suggesting a loss of pathway inhibition in benign tumorigenesis. Although GLI1 and STAT3 exhibited higher median fold changes in the LG-MEC group, these did not reach statistical significance ( p = .151 and p = .158, respectively), likely due to the limited sample size. Conclusion: Our findings identify SUFU deregulation as a potential molecular event in the pathogenesis of PA. The lack of significant SHH and STAT3 differentiation between benign and malignant cohorts suggests that canonical pathway activation may be supplemented by complex regulatory feedbacks. These results provide a molecular foundation for larger-scale proteomic validation of the SHH pathway as a diagnostic or therapeutic target in salivary gland oncology.