Bak is a pro-apoptotic member of the Bcl-2 family of genes that are involved in regulation of programmed cell death. By means of immunohistochemical methods, Bak expression was evaluated in formalin-fixed, paraffin-embedded diagnostic specimens from 83 patients with T1-T4 oral tongue squamous cell carcinomas (SCC). The fractions of tumor cells expressed Bak and their staining intensities were given an expression score. Bak expression was compared with our previous investigated apoptosis-related parameters such as apoptotic index (AI), Bax and Bcl-2 expression, and p53 accumulation. Bak expression correlated positively with Bcl-2 expression (p=0.0001). No significant correlation was found between Bak expression and Bax expression, AI, or p53 accumulation. Patients with Bak expression exceeding the mean value had poorer disease-specific survival when compared with those with values below the mean Bak expression (p=0.01). Cox proportional hazards regression analysis revealed that Bak expression was a significant, independent prognostic variable (p=0.0325). A two-parameter combination of Bak expression and Bax expression, AI, or p53 accumulation revealed an enhanced prognostic potential (p<0.0001) when compared with single parameters. We conclude that Bak expression, particularly in combination with Bax expression, as well as in combination with AI, or p53 accumulation, has prognostic value in tongue SCC.

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