title: FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
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.
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. danielarusso83@yahoo.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy. francesco.merolla@unimol.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Merolla
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. mmascol@gmail.com.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mascolo
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. gennaro.ilardi@gmail.com.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ilardi
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University "Federico II", 80131 Naples, Italy. romanos@dbbm.unina.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Romano
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. silvia.varricchio@gmail.com.
authors.forename: Silvia
authors.initials: S
authors.lastname: Varricchio
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. virnap87@hotmail.it.
authors.forename: Virginia
authors.initials: V
authors.lastname: Napolitano
authors.affiliation: Institute for the Experimental Endocrinology and Oncology, Research National Council, 80131 Naples, Italy. celetti@unina.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Celetti
authors.affiliation: Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research, University "Federico II", 80131 Naples, Italy. loredana.postiglione@unina.it.
authors.forename: Loredana
authors.initials: L
authors.lastname: Postiglione
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. pierpaolo.dilorenzo@unina.it.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Lorenzo
authors.affiliation: Department of Maxillofacial Surgery, University "Federico II", 80131 Naples, Italy. califano@unina.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Califano
authors.affiliation: Department of Maxillofacial Surgery, University "Federico II", 80131 Naples, Italy. giovanni.dellaversanaorabona@unina.it.
authors.forename: Giovanni Orabona
authors.initials: GO
authors.lastname: Dell'Aversana
authors.affiliation: Department of Maxillofacial Surgery, University "Federico II", 80131 Naples, Italy. dottastarita@gmail.com.
authors.forename: Fabio
authors.initials: F
authors.lastname: Astarita
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University "Federico II", 80131 Naples, Italy. mariafiammetta.romano@unina.it.
authors.forename: Maria Fiammetta
authors.initials: MF
authors.lastname: Romano
authors.affiliation: Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy. staibano@unina.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D052162:Human papillomavirus 16 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Bayes theorem; FKBP51; immunotherapy; oral cancer; prognosis; squamous cell carcinoma