Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma.

SRY-box 9 (SOX9), a key transcription factor that regulates chondrocyte differentiation and sex determination, is also involved in the progression of various types of human cancer. However, its function in oral squamous cell carcinoma (OSCC) remains elusive. The purpose of this study was to investigate the expression profiles of SOX9 in oral epithelial lesions, including OSCC. We examined surgical specimens of OSCC that simultaneously contained different grades of epithelial lesions, as assessed by immunohistochemistry for SOX9. The correlation between the expression profiles of SOX9 and the clinicopathological factors was statistically analyzed. We also performed immunofluorescent staining, Western blot analysis, and real-time reverse transcription-polymerase chain reaction for SOX9 using OSCC cell lines, HSC-3 (a metastatic cell line), and HSC-4 (a non-metastatic cell line). On the surgical specimens, SOX9 positivity in the nuclei of proliferating cells was detected in areas with epithelial dysplasia and carcinoma in-situ, but not in areas with normal epithelia. Most of the SCC cells showed nuclear positivity for SOX9. Interestingly, cytoplasmic SOX9 expression was confirmed only in some portions of SCC cells; moreover, an increased proportion of cytoplasmic SOX9 positivity was significantly correlated with worse clinical outcomes. The expression of SOX9 in mRNA and its protein levels were much higher in HSC-3 than in HSC-4, and the cytoplasmic localization of SOX9 expression was confirmed only in HSC-3. In conclusion, SOX9 might be involved in the tumorigenesis and progression of OSCC. Furthermore, the cytoplasmic expression of SOX9 is a potentially useful marker for predicting tumor aggressiveness and the prognosis of OSCC.