Expression of Bcl-2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma

Expression of Bcl-2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma Aims: To characterize the expression of proteins that inhibit (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1) or promote (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA) apoptosis and determine possible correlations between the expression of these proteins and clinicopathological features of oral squamous cell carcinoma (OSCC). Methods and results: Two-hundred and twenty-nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analysed. The results demonstrated that the absence of vascular invasion was associated with increased expression of Bak, Bax, Bcl-xL, Bcl-2-related protein and PUMA. Increased expression of Bim/Bod and BAG-1 was associated with the presence of perineural infiltration. An increase in Bid and Bim-Long expression was associated with moderately to well-differentiated tumours. Increased expression of the Bcl-2-related protein and PUMA was associated with tumours occurring in the floor of mouth and increased expression of PUMA was also associated with recurrence of the tumour. Multivariate Cox analysis demonstrated that PUMA and Bim-Long were independent factors in prognosis of OSCC. Conclusions: Our results showed the involvement of the Bcl-2 family of proteins in OSCC tumorigenesis and suggest that the expression of apoptotic molecules might be used as a prognostic indicator for OSCC.