Immunohistochemical expression of Bid in oral squamous cell carcinoma

Abstract

Bcl-2 and its congeners play a key role in controlling programmed cell death (PCD, apoptosis). We and others have reported the status of anti-PCD proto-oncogenes Bcl-2, Bcl-X L , Mcl-1, and Bag-1 as well as Bax and Bak (pro-PCD) in oral cancer. The objective of this study was to examine the expression of Bid (allosteric regulator) in oral carcinomas. For this purpose, 5 micron-thick sections from archival paraffin blocks were examined using polyclonal antibodies to Bid oncoprotein. A finely granular Bid immunoreactivity was observed primarily in the cytoplasm of 60% (12 out of 20) of the carcinomas. A varying degree of zonal or diffuse heterogenous reaction was observed generally based on the degree of neoplastic cell differentiation. The mechanisms involving the role of Bid in regulation of apoptosis remain unclear. It has been considered that: (1) full-length Bid translocates Bax to the outer mitochondrial membrane and Bax activation results in induction of mitochondrial permeability transition, (2) caspase 8–cleaved Bid (t-Bid) induces conformational change in Bak, and (3) other mechanisms. These processes enable cytochrome-c release from mitochondria. Cytochrome-c forms apoptosome with caspase 9 leading to caspase activation. Initiating caspases 9 and 8 activate downstream caspase 3, leading to apoptosis. It appears that Bid plays an effector role by inducing functional status to other oncogenes. The elucidation of Bid in oral carcinomas as well as caspases 8 and 3 (previously reported by us) indicate a potential for apoptosis. A higher apoptotic index has been shown to confer favorable response to treatment; therefore, the induction of apoptosis (inherent in tumor cells) could be a valuable tool for oral cancer therapy.