Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

New Immunohistochemical Markers for Pleural Mesothelioma Subtyping

Iosè Di Stefano
ORCID logo ,
Greta Alì
* ,
Anello Marcello Poma
,
Rossella Bruno
,
Agnese Proietti
,
Cristina Niccoli
,
Carmelina Cristina Zirafa
ORCID logo ,
Franca Melfi
ORCID logo ,
Maria Giovanna Mastromarino
ORCID logo ,
Marco Lucchi
ORCID logo ,
Gabriella Fontanini
Version 1 : Received: 2 August 2023 / Approved: 3 August 2023 / Online: 4 August 2023 (12:34:31 CEST)

A peer-reviewed article of this Preprint also exists.

Di Stefano, I.; Alì, G.; Poma, A.M.; Bruno, R.; Proietti, A.; Niccoli, C.; Zirafa, C.C.; Melfi, F.; Mastromarino, M.G.; Lucchi, M.; Fontanini, G. New Immunohistochemical Markers for Pleural Mesothelioma Subtyping. Diagnostics 2023, 13, 2945. Di Stefano, I.; Alì, G.; Poma, A.M.; Bruno, R.; Proietti, A.; Niccoli, C.; Zirafa, C.C.; Melfi, F.; Mastromarino, M.G.; Lucchi, M.; Fontanini, G. New Immunohistochemical Markers for Pleural Mesothelioma Subtyping. Diagnostics 2023, 13, 2945.

Abstract

Pleural mesothelioma (PM) comprises three main subtypes: epithelioid, biphasic and sarcomatoid, which have a different impact 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 a good sensitivity (79% and 84%) and specificity (84% and 73%) for the epithelioid subtype. CFB and PAK4 had an inferior performance, with higher sensitivity (89% and 84%), but lower specificity (64% and 36%). In the biphasic group, all markers showed a 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.

Keywords

pleural mesothelioma; subtypes; immunohistochemistry; Mesothelin; Claudin-15; Complement Factor B (CFB); Plasminogen Activator Inhibitor 1 (PAI1); p21-activated kinase 4 (PAK4).

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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