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FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?

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 st...

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Autores principales: Russo, Daniela, Merolla, Francesco, Mascolo, Massimo, Ilardi, Gennaro, Romano, Simona, Varricchio, Silvia, Napolitano, Virginia, Celetti, Angela, Postiglione, Loredana, Di Lorenzo, Pier Paolo, Califano, Luigi, Dell’Aversana, Giovanni Orabona, Astarita, Fabio, Romano, Maria Fiammetta, Staibano, Stefania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343977/
https://www.ncbi.nlm.nih.gov/pubmed/28218707
http://dx.doi.org/10.3390/ijms18020443
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author Russo, Daniela
Merolla, Francesco
Mascolo, Massimo
Ilardi, Gennaro
Romano, Simona
Varricchio, Silvia
Napolitano, Virginia
Celetti, Angela
Postiglione, Loredana
Di Lorenzo, Pier Paolo
Califano, Luigi
Dell’Aversana, Giovanni Orabona
Astarita, Fabio
Romano, Maria Fiammetta
Staibano, Stefania
author_facet Russo, Daniela
Merolla, Francesco
Mascolo, Massimo
Ilardi, Gennaro
Romano, Simona
Varricchio, Silvia
Napolitano, Virginia
Celetti, Angela
Postiglione, Loredana
Di Lorenzo, Pier Paolo
Califano, Luigi
Dell’Aversana, Giovanni Orabona
Astarita, Fabio
Romano, Maria Fiammetta
Staibano, Stefania
author_sort Russo, Daniela
collection PubMed
description 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.
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spelling pubmed-53439772017-03-16 FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC? Russo, Daniela Merolla, Francesco Mascolo, Massimo Ilardi, Gennaro Romano, Simona Varricchio, Silvia Napolitano, Virginia Celetti, Angela Postiglione, Loredana Di Lorenzo, Pier Paolo Califano, Luigi Dell’Aversana, Giovanni Orabona Astarita, Fabio Romano, Maria Fiammetta Staibano, Stefania Int J Mol Sci Article 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. MDPI 2017-02-18 /pmc/articles/PMC5343977/ /pubmed/28218707 http://dx.doi.org/10.3390/ijms18020443 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Russo, Daniela
Merolla, Francesco
Mascolo, Massimo
Ilardi, Gennaro
Romano, Simona
Varricchio, Silvia
Napolitano, Virginia
Celetti, Angela
Postiglione, Loredana
Di Lorenzo, Pier Paolo
Califano, Luigi
Dell’Aversana, Giovanni Orabona
Astarita, Fabio
Romano, Maria Fiammetta
Staibano, Stefania
FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
title FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
title_full FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
title_fullStr FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
title_full_unstemmed FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
title_short FKBP51 Immunohistochemical Expression: A New Prognostic Biomarker for OSCC?
title_sort fkbp51 immunohistochemical expression: a new prognostic biomarker for oscc?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343977/
https://www.ncbi.nlm.nih.gov/pubmed/28218707
http://dx.doi.org/10.3390/ijms18020443
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