Head and Neck Cancers (HNCs) comprise a wide range of neoplasms originating from the lining epithelium of head and neck district, mainly squamous cell carcinomas of the oral cavity (OSCC). OSCC is mostly associated to tobacco and to alcohol abuse and recently to persistent Human Papillomavirus (HPV) infection (in particular, restricted to the oropharyngeal region). Whereas HPV-related OSCC are characterized by a significantly slow progression and high response to chemo- and radiotherapy, the “HPV-unrelated OSCC are intrinsically highly aggressive and almost always chemo- and radio resistant. To date, there is still an urgent need for new prognostic and predictive biomarkers, for these deadly cancers. In fact, oppositely to that occurring in HPV-positive oropharyngeal squamous cell cancer, there are no reliable prognostic or predictive biomarkers for non-oropharyngeal SCC.
Recently, we demonstrated that the native (full-length) form of the FKBP51 protein may have a role in biological aggressiveness of skin melanoma and OSCC.
FKBP51 is a member of the FK506 binding proteins, a family of immunophilins, that is targetable by immunosuppressive drugs such as rapamycin and tacrolimus. For this reason, this protein is emerging as a very interesting new target for cancer immunotherapy.
The present study has been focused on the possible biological significance of the tissue immunohistochemical expression of the short splice variant of the gene FKBP5 (FKBP5s), in immunoediting and biological behavior of OSCC.
Our OSCC study population included 49 cases, 20 males and 29 females (mean age 64.5 years, median 66 years). The statistical analysis of the expression of FKBP51s evidenced that 93.3% (14/15) of cancers with poor outcome registered at follow-up showed significantly strong immunostaining on the tumor invasion front. By converse, all the pre-neoplastic lesional areas with medium degree dysplasia were found negative for FKBP51s, whereas in the case of severe dysplasia and in situ carcinomas we found an exclusively nuclear staining for the protein, progressively shifting toward cytoplasm exclusively in micro invasive areas.
These results support the hypothesis of a role for either FKBP51 and FKBP51s as new progression markers, easily detectable by immunohistochemistry at the time of the first diagnosis. In addition, they can significantly contribute to the better risk stratification of patients with OSCC. Finally, our results lead us to postulate that the introduction of selective FKBP51 inhibitors (either for FKBP51 and FKBP51s) may directly counteract tumor aggressiveness of OSCC and provide also new useful tools for new immunotherapy regimens
