Sonic Hedgehog as a Potential Indicator of Tumor Progression in Tongue Squamous Cell Carcinoma

Abstract

Background: Tongue squamous cell carcinoma (TSCC) is the most prevalent form of oral cancer. Despite advances in surgery, radiotherapy, and chemotherapy, the 5-year survival rate remains poor due to local recurrence and regional metastasis following treatment. The Sonic Hedgehog (SHH) signaling pathway is essential for differentiation, proliferation, and tissue maintenance, and its deregulation is implicated in various neoplasms. Objectives: This study aimed to evaluate the expression of SHH protein in TSCC patients and compare it with normal tissue samples. Methods: In this cross-sectional study, a total of 36 TSCC cases (grades I, II, and III) and 12 normal tissue samples from the archives of Mashhad School of Dentistry were analyzed. Only samples with sufficient residual tissue and without autolysis or inadequate material for immune histochemistry (IHC) were selected for the final analysis. Immunohistochemical staining was performed using the SHH marker. Positive cases were scored based on the percentage of immunoreactive cells. Statistical analyses were conducted to compare SHH expression between groups. Results: The SHH protein expression in the cytoplasm differed significantly between normal tissue and TSCC grades I, II, and III (P < 0.001). Pairwise comparisons showed significantly higher SHH expression in grade II (P = 0.002) and grade III (P < 0.001) compared to normal tissue. Moreover, grade III TSCC exhibited greater SHH expression than grade I (P < 0.001). Conclusions: The SHH protein expression correlates positively with the histological grade of TSCC, suggesting a critical role for SHH in the carcinogenesis and progression of TSCC.