New Immunohistochemical Markers for Pleural Mesothelioma Subtyping

Pleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have different impacts on prognosis and treatment definition. However, PM subtyping can be complex given the inter- and intra-tumour morphological heterogeneity. We aim to use immunohistochemistry (...

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Main Authors: Iosè Di Stefano, Greta Alì, Anello Marcello Poma, Rossella Bruno, Agnese Proietti, Cristina Niccoli, Carmelina Cristina Zirafa, Franca Melfi, Maria Giovanna Mastromarino, Marco Lucchi, Gabriella Fontanini
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语言:English
出版: MDPI AG 2023-09-01
丛编:Diagnostics
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在线阅读:https://www.mdpi.com/2075-4418/13/18/2945
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author Iosè Di Stefano
Greta Alì
Anello Marcello Poma
Rossella Bruno
Agnese Proietti
Cristina Niccoli
Carmelina Cristina Zirafa
Franca Melfi
Maria Giovanna Mastromarino
Marco Lucchi
Gabriella Fontanini
author_facet Iosè Di Stefano
Greta Alì
Anello Marcello Poma
Rossella Bruno
Agnese Proietti
Cristina Niccoli
Carmelina Cristina Zirafa
Franca Melfi
Maria Giovanna Mastromarino
Marco Lucchi
Gabriella Fontanini
author_sort Iosè Di Stefano
collection DOAJ
description Pleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have different impacts on prognosis and treatment definition. However, PM subtyping can be complex given the inter- and intra-tumour morphological heterogeneity. We aim to use immunohistochemistry (IHC) to evaluate five markers (Mesothelin, Claudin-15, Complement Factor B, Plasminogen Activator Inhibitor 1 and p21-activated Kinase 4), whose encoding genes have been previously reported as deregulated among PM subtypes. Immunohistochemical expressions were determined in a case series of 73 PMs, and cut-offs for the epithelioid and non-epithelioid subtypes were selected. Further validation was performed on an independent cohort (30 PMs). For biphasic PM, the percentage of the epithelioid component was assessed, and IHC evaluation was also performed on the individual components separately. Mesothelin and Claudin-15 showed good sensitivity (79% and 84%) and specificity (84% and 73%) for the epithelioid subtype. CFB and PAK4 had inferior performance, with higher sensitivity (89% and 84%) but lower specificity (64% and 36%). In the biphasic group, all markers showed different expression when comparing epithelioid with sarcomatoid areas. Mesothelin, Claudin-15 and CFB can be useful in subtype discrimination. PAI1 and PAK4 can improve component distinction in biphasic PM.
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spelling doaj.art-2946ea5f228745a8956b5b11e79a07902023-11-19T10:13:46ZengMDPI AGDiagnostics2075-44182023-09-011318294510.3390/diagnostics13182945New Immunohistochemical Markers for Pleural Mesothelioma SubtypingIosè Di Stefano0Greta Alì1Anello Marcello Poma2Rossella Bruno3Agnese Proietti4Cristina Niccoli5Carmelina Cristina Zirafa6Franca Melfi7Maria Giovanna Mastromarino8Marco Lucchi9Gabriella Fontanini10Surgical, Medical, Molecular, and Critical Care Pathology Department, University of Pisa, 56126 Pisa, ItalySurgical, Medical, Molecular, and Critical Care Pathology Department, University of Pisa, 56126 Pisa, ItalySurgical, Medical, Molecular, and Critical Care Pathology Department, University of Pisa, 56126 Pisa, ItalyUnit of Pathological Anatomy, University Hospital of Pisa, 56126 Pisa, ItalyUnit of Pathological Anatomy, University Hospital of Pisa, 56126 Pisa, ItalyUnit of Pathological Anatomy, University Hospital of Pisa, 56126 Pisa, ItalyMultispecialty Centre for Surgery, Minimally Invasive and Robotic Thoracic Surgery, University Hospital of Pisa, 56100 Pisa, ItalyMultispecialty Centre for Surgery, Minimally Invasive and Robotic Thoracic Surgery, University Hospital of Pisa, 56100 Pisa, ItalyUnit of Thoracic Surgery, University Hospital of Pisa, 56126 Pisa, ItalyUnit of Thoracic Surgery, University Hospital of Pisa, 56126 Pisa, ItalySurgical, Medical, Molecular, and Critical Care Pathology Department, University of Pisa, 56126 Pisa, ItalyPleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have different impacts on prognosis and treatment definition. However, PM subtyping can be complex given the inter- and intra-tumour morphological heterogeneity. We aim to use immunohistochemistry (IHC) to evaluate five markers (Mesothelin, Claudin-15, Complement Factor B, Plasminogen Activator Inhibitor 1 and p21-activated Kinase 4), whose encoding genes have been previously reported as deregulated among PM subtypes. Immunohistochemical expressions were determined in a case series of 73 PMs, and cut-offs for the epithelioid and non-epithelioid subtypes were selected. Further validation was performed on an independent cohort (30 PMs). For biphasic PM, the percentage of the epithelioid component was assessed, and IHC evaluation was also performed on the individual components separately. Mesothelin and Claudin-15 showed good sensitivity (79% and 84%) and specificity (84% and 73%) for the epithelioid subtype. CFB and PAK4 had inferior performance, with higher sensitivity (89% and 84%) but lower specificity (64% and 36%). In the biphasic group, all markers showed different expression when comparing epithelioid with sarcomatoid areas. Mesothelin, Claudin-15 and CFB can be useful in subtype discrimination. PAI1 and PAK4 can improve component distinction in biphasic PM.https://www.mdpi.com/2075-4418/13/18/2945pleural mesotheliomasubtypesimmunohistochemistryMesothelinClaudin-15Complement Factor B (CFB)
spellingShingle Iosè Di Stefano
Greta Alì
Anello Marcello Poma
Rossella Bruno
Agnese Proietti
Cristina Niccoli
Carmelina Cristina Zirafa
Franca Melfi
Maria Giovanna Mastromarino
Marco Lucchi
Gabriella Fontanini
New Immunohistochemical Markers for Pleural Mesothelioma Subtyping
Diagnostics
pleural mesothelioma
subtypes
immunohistochemistry
Mesothelin
Claudin-15
Complement Factor B (CFB)
title New Immunohistochemical Markers for Pleural Mesothelioma Subtyping
title_full New Immunohistochemical Markers for Pleural Mesothelioma Subtyping
title_fullStr New Immunohistochemical Markers for Pleural Mesothelioma Subtyping
title_full_unstemmed New Immunohistochemical Markers for Pleural Mesothelioma Subtyping
title_short New Immunohistochemical Markers for Pleural Mesothelioma Subtyping
title_sort new immunohistochemical markers for pleural mesothelioma subtyping
topic pleural mesothelioma
subtypes
immunohistochemistry
Mesothelin
Claudin-15
Complement Factor B (CFB)
url https://www.mdpi.com/2075-4418/13/18/2945
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