Abstract
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients’ risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors. We already investigated the role of the immune modulator FK506-binding protein 51 (FKBP51), a FK506-binding immunophilin, in cutaneous melanoma biology, and its expression in several human solid tumors. In the present study, we aimed to assess the value of FKBP51 expression in OSCC tumor cells as a marker of outcome. We collected clinical data from 72 patients who underwent surgery for Squamous Cell Carcinoma (SCC) of the tongue, floor, lips and palate. FKBP51 expression was assessed by immunohistochemistry on paraffin-embedded tumor tissues. In addition, we evaluated the human papillomavirus (HPV) status of primary tumors by immunohistochemistry, viral subtyping and In Situ Hybridization (ISH) assay. We found that high FKBP51-expressing tumors characterized the OSCCs with the worst prognosis: the high immunohistochemical expression of FKBP51 associated with death occurring within five years from the diagnosis with a sensitivity of 88.46% and a specificity of 91.67%. The estimated positive predictive value of the test was 88.45% and negative predictive value 91.67%. We tested FKBP51 mRNA presence, by RT-PCR assay, in a selected series of OSCC tumors, and we found that mRNA correlated well to the protein expression and to the clinical outcome. Applying the Bayes formula, we estimated an 88% probability of dying within five years from the diagnosis of OSCC patients with a high FKBP51 immunohistochemical (IHC) test result (>51% of FKBP51 positive tumor cells). On the basis of our analysis, we propose tumor tissue expression of FKBP51 protein as a reliable prognostic marker for OSCC tumors.
Highlights
Head and neck cancers (HNCs) include a broad range of malignancies that mainly originate from the lining epithelium of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx and larynx and mostly consist of squamous cell carcinomas (head and neck squamous cell carcinoma (HNSCC)) [1]
According to the national cancer registry data, in Italy, there will be about 10,000 new head and neck cancer cases in 2016; the risk of developing a tumor is much higher in males than females; and the prevalence of the disease is higher than 100,000 cases per year [4]
We found a significant correlation between FK506-binding protein 51 (FKBP51) expression and outcome of the oral squamous cell carcinomas
Summary
Head and neck cancers (HNCs) include a broad range of malignancies that mainly originate from the lining epithelium of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx and larynx and mostly consist of squamous cell carcinomas (head and neck squamous cell carcinoma (HNSCC)) [1]. Squamous cell carcinomas of the oral cavity (OSCC) represent the most frequent forms of HNSCCs. About 50,000 new cases of oral cancers and 10,000 deaths have been estimated in 2016 in the USA; the global incidence is about 300,000 new cases per year with an annual mortality rate of about 145,000, Melanesia, South-Central Asia and Central-Eastern Europe accounting for the highest rates [2,3]. The exposure to classical causative agents such as alcohol and tobacco remains the largest risk factor for squamous cancers of the aerodigestive tract, a rapid expansion of OSCC related to oncogenic HPV infection is still occurring, whose spreading in some regions has been referred to as epidemic [3]. In 2020 in the USA, it is expected that the annual incidence of HNCs will surpass that of the cervical cancer related to HPV infection
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