Prognostic Implications of SOX2^low/Ki-67^high in Oral Squamous Cell Carcinoma

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We aimed to clarify the prognostic significance of SRY-box transcription factor 2 (SOX2) expression in oral squamous cell carcinoma (OSCC) and to evaluate its relationship with tumor proliferative activity assessed by Ki-67. We included 42 patients with OSCC who underwent surgical resection. Immunohistochemical staining for SOX2 and Ki-67 was performed using formalin-fixed, paraffin-embedded specimens; subsequently, labeling indices were evaluated. We analyzed the relationships between immunohistochemical expression patterns and clinicopathological factors; further, we assessed overall survival (OS) and disease-free survival (DFS) using Kaplan–Meier analysis and Cox proportional hazards models. In the univariate analysis, SOX2 expression alone showed a non-significant trend toward poorer OS; however, it was not an independent prognostic factor in multivariate analysis. Ki-67 expression was not significantly associated with OS; however, high Ki-67 expression emerged as the only independent prognostic factor for DFS. Notably, patients with a combined SOX2-low/Ki-67-high immunophenotype showed significantly worse OS than those with other immunophenotypes; moreover, this combination remained an independent prognostic factor for OS together with clinical stage. Taken together, our findings indicate that combined immunohistochemical evaluation of SOX2 and Ki-67 can identify a biologically aggressive subgroup of OSCC. Therefore, integration of differentiation- and proliferation-related markers may improve prognostic stratification beyond conventional clinicopathological assessment in OSCC.