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Open AccessArticle

FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?

Department of Advanced Biomedical Sciences, University “Federico II”, 80131 Naples, Italy
Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, 86100 Campobasso, Italy
Department of Molecular Medicine and Medical Biotechnology, University “Federico II”, 80131 Naples, Italy
Institute for the Experimental Endocrinology and Oncology, Research National Council, 80131 Naples, Italy
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research, University “Federico II”, 80131 Naples, Italy
Department of Maxillofacial Surgery, University “Federico II”, 80131 Naples, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2017, 18(2), 443;
Received: 29 December 2016 / Revised: 3 February 2017 / Accepted: 9 February 2017 / Published: 18 February 2017
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. View Full-Text
Keywords: FKBP51; oral cancer; prognosis; immunotherapy; Bayes theorem; squamous cell carcinoma FKBP51; oral cancer; prognosis; immunotherapy; Bayes theorem; squamous cell carcinoma
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Russo, D.; Merolla, F.; Mascolo, M.; Ilardi, G.; Romano, S.; Varricchio, S.; Napolitano, V.; Celetti, A.; Postiglione, L.; Di Lorenzo, P.P.; Califano, L.; Dell’Aversana, G.O.; Astarita, F.; Romano, M.F.; Staibano, S. FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC? Int. J. Mol. Sci. 2017, 18, 443.

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