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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MDPI AG
2023-09-01
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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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issn | 2075-4418 |
language | English |
last_indexed | 2024-03-10T22:51:55Z |
publishDate | 2023-09-01 |
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series | Diagnostics |
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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