Clinicopathologic significance of Sox2, CD44 and CD44v6 expression in intrahepatic cholangiocarcinoma

Embryonic stem cells (ESC) and cancer stem cells (CSC) have a capacity for self-renewal and differentiation into multiple cell lineages. Sox2 plays a critical role in ESC and has been shown to participate in carcinogenesis and tumor progression in many human cancers. CD44 and CD44v6 are putative CSC markers and their association with tumor progression, metastasis, and tumor relapse after treatment has been demonstrated. We evaluated the immunoexpression of Sox2, CD44, and CD44v6 in 85 cases of Intrahepatic cholangiocarcinomas (IHCC) and assessed their prognostic significance. Sox2 expression showed a significant association with lymph node metastasis (p = 0.025), T4 stage (p = 0.046), and worse overall survival (p = 0.047). Greater expression of Sox2 was observed in IHCC with poor differentiation, vascular invasion, and stage IV, without statistical significance (p > 0.05). CD44 expression showed an association with periductal infiltrative type (p = 0.034), poor differentiation (p = 0.012), and vascular invasion (p = 0.009). CD44v6 expression was evident in patients with stage IV (p = 0.019). These results demonstrated that Sox2 expression is associated with aggressive behavior and poor overall survival in IHCC.