TRAIL plays an important role in host immunosurveillance against tumor metastasis, induces apoptosis of tumor cells but not normal cells, and thus has great therapeutic potential for cancer treatment. TRAIL binds to two cell death-inducing (DR4 and DR5) and two decoy (DcR1, and DcR2) receptors. Therefore, it has been suggested that differential expression of death versus decoy receptors determines the sensitivity of tumor cells to TRAIL. We therefore elected to correlate the expression levels of TRAIL and its receptors in OSCC with the apoptosis rate in tumor cells and tumor-infiltrating lymphocytes (TIL) and with various clinicopathologic prognostic parameters. expression of TRAIL and its receptors was studied immunohistochemically (IHC) in archival specimens of OSCC (n=42) and their mRNA expression was confirmed by RT-PCR in selected cases. Apoptosis rates of tumor cells and TIL were determined by IHC detection of cleaved caspase 3. Caspase 3 labeling index (LI; %) among tumor cells and TIL were assessed using an ImagePro Plus analysis system. expression levels of TRAIL receptors in tumor cells were graded semiquantitatively. TRAIL is constitutively expressed in normal oral mucosa but its expression is almost completely lost in OSCC. OSCC frequently expressed high levels (>75% positive tumor cells) of DcR1, followed by DR4, DR5 and DcR2 in 76%, 66%, 25% and 5% of OSCC cases, respectively. expression of each receptor in OSCC is mostly determined by whether or not this receptor is expressed in uninvolved oral mucosa. There were no significant differences in the expression levels of each of these receptors among uninvolved oral mucosa, primary and metastatic tumors of the same patient. DR5 expression was significantly associated with larger tumor size (T3/4). Expression levels of TRAIL and its receptors failed to show any statistically significant correlation with the following clinical and histopathologic parameters: histologic grade; lymph node status; apoptosis rate of tumor cells and TIL. Differential expression of death versus decoy TRAIL receptors in OSCC does not appear to play a role either in their apoptosis rate or metastatic progression. Therefore, resistance of OSCC cells to TRAIL-induced apoptosis is controlled by some other mechanism and not by the expression levels of its receptors.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]