SOX-2 and EZH-2 Expression in Primary Epithelial Malignant Salivary Gland Tumors

Malignant salivary gland tumors represent a highly diverse group of neoplasms, their heterogeneity likely arising due to variable origin in different tissue components. Emerging evidence suggests that SOX-2 and EZH-2 play critical roles in salivary gland carcinogenesis, being related to tumor cell stemness potential, along with accelerated tumor progression and unfavorable clinical outcomes. The aim of this study was to assess the association between SOX-2 and EZH-2 expression, survival parameters, and tumors' pathological characteristics in a group of patients with primary epithelial malignant salivary gland tumors (MSGTs) and to evaluate their value as diagnostic and prognostic markers.

Our study group comprised 104 patients with primary epithelial MSGTs diagnosed in "Sf. Spiridon" County Hospital, Iasi, over a period of fifteen years. Pathological parameters and survival evaluation, along with SOX-2 and EZH-2 immunohistochemistry assessment and scoring, were conducted, and the associations between different parameters were analyzed.

High SOX-2 immunoexpression was significantly associated with lymphatic invasion (LY) (p = 0.003), pT stage (p = 0.010), histological tumor type (p = 0.003), and tumor grading (p = 0.037), while high EZH-2 immunoexpression was significantly associated with perineural invasion (PnI) (p < 0.001), vascular invasion (p = 0.038), LY (p = 0.001), tumor grading (p = 0.002), and pathological extranodal extension (pENE) (p = 0.018). The tumors with high SOX-2 and EZH-2 expressions were associated with a reduced overall survival (OS) (p = 0.013 and p = 0.011). Cox regression analysis revealed that pT (HR = 1.826, p = 0.019), LY (HR = 0.318, p = 0.007), and tumor grade (HR = 0.505, p = 0.021) added to high SOX-2 and EZH-2 immunoexpression independently predicted a poor survival outcome (HR = 2.373, p = 0.016 and HR = 2.746, p = 0.015).

Our findings suggest that SOX-2 and EZH-2 may serve as biomarkers of aggressive behavior and a poor prognosis in primary epithelial MSGTs, providing potential opportunities for precision-targeted therapies.