The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer

Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however...

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Main Authors: Tatiana Cano Barbadilla, Martina Álvarez Pérez, Juan Daniel Prieto Cuadra, Mª Teresa Dawid de Vera, Fernando Alberca-del Arco, Isabel García Muñoz, Rocío Santos-Pérez de la Blanca, Bernardo Herrera-Imbroda, Elisa Matas-Rico, Mª Isabel Hierro Martín
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/14/22/2501
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author Tatiana Cano Barbadilla
Martina Álvarez Pérez
Juan Daniel Prieto Cuadra
Mª Teresa Dawid de Vera
Fernando Alberca-del Arco
Isabel García Muñoz
Rocío Santos-Pérez de la Blanca
Bernardo Herrera-Imbroda
Elisa Matas-Rico
Mª Isabel Hierro Martín
author_facet Tatiana Cano Barbadilla
Martina Álvarez Pérez
Juan Daniel Prieto Cuadra
Mª Teresa Dawid de Vera
Fernando Alberca-del Arco
Isabel García Muñoz
Rocío Santos-Pérez de la Blanca
Bernardo Herrera-Imbroda
Elisa Matas-Rico
Mª Isabel Hierro Martín
author_sort Tatiana Cano Barbadilla
collection DOAJ
description Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains limited due to the high costs and complexity of genomic techniques. This review examines the role of immunohistochemistry (IHC) as a surrogate marker for molecular subtyping in BC, highlighting its potential to bridge the gap between advanced molecular classifications and routine clinical application; Methods: We explore the evolution of taxonomic classification in BC, with a particular focus on cytokeratin (KRT) expression patterns in normal urothelium, which are key to identifying basal and luminal subtypes. Furthermore, we emphasise the need for consensus on IHC markers to reliably define these subtypes, facilitating wider and standardised clinical use. The review also analyses the application of IHC in both muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC), with particular attention to the less extensively studied NMIBC cases. We discuss the practical advantages of IHC for subtyping, including its cost effectiveness and feasibility in standard pathology laboratories, alongside ongoing challenges such as the requirement for standardised protocols and external validation across diverse clinical settings; Conclusions: While IHC has limitations, it offers a viable alternative for laboratories lacking access to advanced molecular techniques. Further research is required to determine the optimal combination of markers, establish a consensus diagnostic algorithm, and validate IHC through large-scale trials. This will ultimately enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes.
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spelling doaj-art-4692fc6d59e94fcf9a8e55f71a6ef0802025-08-20T02:28:12ZengMDPI AGDiagnostics2075-44182024-11-011422250110.3390/diagnostics14222501The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder CancerTatiana Cano Barbadilla0Martina Álvarez Pérez1Juan Daniel Prieto Cuadra2Mª Teresa Dawid de Vera3Fernando Alberca-del Arco4Isabel García Muñoz5Rocío Santos-Pérez de la Blanca6Bernardo Herrera-Imbroda7Elisa Matas-Rico8Mª Isabel Hierro Martín9Pathology Department, Juan Ramón Jiménez University Hospital (HJRJ), 21005 Huelva, SpainDepartment of Human Physiology, Human Histology, Pathology, and Sports Physical Education, University of Malaga (UMA), 29071 Málaga, SpainDepartment of Human Physiology, Human Histology, Pathology, and Sports Physical Education, University of Malaga (UMA), 29071 Málaga, SpainDepartment of Human Physiology, Human Histology, Pathology, and Sports Physical Education, University of Malaga (UMA), 29071 Málaga, SpainInstitute of Biomedical Research in Malaga (IBIMA-Plataforma BIONAND), 29590 Málaga, SpainDepartment of Human Physiology, Human Histology, Pathology, and Sports Physical Education, University of Malaga (UMA), 29071 Málaga, SpainInstitute of Biomedical Research in Malaga (IBIMA-Plataforma BIONAND), 29590 Málaga, SpainInstitute of Biomedical Research in Malaga (IBIMA-Plataforma BIONAND), 29590 Málaga, SpainInstitute of Biomedical Research in Malaga (IBIMA-Plataforma BIONAND), 29590 Málaga, SpainDepartment of Human Physiology, Human Histology, Pathology, and Sports Physical Education, University of Malaga (UMA), 29071 Málaga, SpainBackground/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains limited due to the high costs and complexity of genomic techniques. This review examines the role of immunohistochemistry (IHC) as a surrogate marker for molecular subtyping in BC, highlighting its potential to bridge the gap between advanced molecular classifications and routine clinical application; Methods: We explore the evolution of taxonomic classification in BC, with a particular focus on cytokeratin (KRT) expression patterns in normal urothelium, which are key to identifying basal and luminal subtypes. Furthermore, we emphasise the need for consensus on IHC markers to reliably define these subtypes, facilitating wider and standardised clinical use. The review also analyses the application of IHC in both muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC), with particular attention to the less extensively studied NMIBC cases. We discuss the practical advantages of IHC for subtyping, including its cost effectiveness and feasibility in standard pathology laboratories, alongside ongoing challenges such as the requirement for standardised protocols and external validation across diverse clinical settings; Conclusions: While IHC has limitations, it offers a viable alternative for laboratories lacking access to advanced molecular techniques. Further research is required to determine the optimal combination of markers, establish a consensus diagnostic algorithm, and validate IHC through large-scale trials. This will ultimately enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes.https://www.mdpi.com/2075-4418/14/22/2501bladder cancerimmunohistochemistrymolecular subtypesmolecular classification
spellingShingle Tatiana Cano Barbadilla
Martina Álvarez Pérez
Juan Daniel Prieto Cuadra
Mª Teresa Dawid de Vera
Fernando Alberca-del Arco
Isabel García Muñoz
Rocío Santos-Pérez de la Blanca
Bernardo Herrera-Imbroda
Elisa Matas-Rico
Mª Isabel Hierro Martín
The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
Diagnostics
bladder cancer
immunohistochemistry
molecular subtypes
molecular classification
title The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
title_full The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
title_fullStr The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
title_full_unstemmed The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
title_short The Role of Immunohistochemistry as a Surrogate Marker in Molecular Subtyping and Classification of Bladder Cancer
title_sort role of immunohistochemistry as a surrogate marker in molecular subtyping and classification of bladder cancer
topic bladder cancer
immunohistochemistry
molecular subtypes
molecular classification
url https://www.mdpi.com/2075-4418/14/22/2501
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