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ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies

SIMPLE SUMMARY: Mounting evidence show that dedifferentiated and undifferentiated endometrial and ovarian carcinomas (DDC/UDC) are clinically distinct entities with rapid progression, poor response to adjuvant therapy, and grim outcome, even when compared to other high-grade gynecologic malignancies...

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Autor principal: Tessier-Cloutier, Basile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486746/
https://www.ncbi.nlm.nih.gov/pubmed/37686505
http://dx.doi.org/10.3390/cancers15174229
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author Tessier-Cloutier, Basile
author_facet Tessier-Cloutier, Basile
author_sort Tessier-Cloutier, Basile
collection PubMed
description SIMPLE SUMMARY: Mounting evidence show that dedifferentiated and undifferentiated endometrial and ovarian carcinomas (DDC/UDC) are clinically distinct entities with rapid progression, poor response to adjuvant therapy, and grim outcome, even when compared to other high-grade gynecologic malignancies. Unfortunately, they are very challenging to diagnose and often receive a non-specific or ambiguous diagnosis. Immunohistochemical tests for core SWI/SNF proteins (i.e. ARID1B, SMARCA4, and SMARCB1) offer high specificity for DDC/UDC, low cost, and fast turnaround time, unlike DNA sequencing-based assays which currently have very limited use in predicting inactivation core SWI/SNF subunits. Recent reports show that among the known core SWI/SNF proteins, ARID1B inactivation are most common in these tumors, yet this test is rarely available even in tertiary centers. In this opinion I stress the importance of including ARID1B along with other core SWI/SNF proteins in the diagnostic workup of DDC/UDC. ABSTRACT: Dedifferentiated and undifferentiated endometrial and ovarian carcinomas (DDC/UDC) are aggressive malignancies defined by morphologic and molecular undifferentiation, and associated with core SWI/SNF deficiency. Their main differential diagnoses include high-grade endometrial and ovarian carcinomas that often show overlapping morphologic and molecular profiles. Loss of cell lineage markers expression by immunohistochemistry (IHC) is commonly used to assist diagnosis, but it has poor specificity, while core SWI/SNF deficiency is much more specific. Approximately half of SWI/SNF-deficient DDC/UDC are associated with loss of ARID1B expression, yet, unlike the other core SWI/SNF proteins (SMARCA4 and SMARCB1), this test is rarely available, even in tertiary centers. Mutational testing for ARID1B is increasingly common among targeted DNA sequencing panels, but it is difficult to interpret in the absence of IHC results. Overall, the importance of including ARID1B IHC as part of the routine panel for undifferentiated gynecologic malignancies should be emphasized, especially as SWI/SNF inactivation is becoming a necessary biomarker for diagnostics, clinical management, and clinical trial enrollment.
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spelling pubmed-104867462023-09-09 ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies Tessier-Cloutier, Basile Cancers (Basel) Opinion SIMPLE SUMMARY: Mounting evidence show that dedifferentiated and undifferentiated endometrial and ovarian carcinomas (DDC/UDC) are clinically distinct entities with rapid progression, poor response to adjuvant therapy, and grim outcome, even when compared to other high-grade gynecologic malignancies. Unfortunately, they are very challenging to diagnose and often receive a non-specific or ambiguous diagnosis. Immunohistochemical tests for core SWI/SNF proteins (i.e. ARID1B, SMARCA4, and SMARCB1) offer high specificity for DDC/UDC, low cost, and fast turnaround time, unlike DNA sequencing-based assays which currently have very limited use in predicting inactivation core SWI/SNF subunits. Recent reports show that among the known core SWI/SNF proteins, ARID1B inactivation are most common in these tumors, yet this test is rarely available even in tertiary centers. In this opinion I stress the importance of including ARID1B along with other core SWI/SNF proteins in the diagnostic workup of DDC/UDC. ABSTRACT: Dedifferentiated and undifferentiated endometrial and ovarian carcinomas (DDC/UDC) are aggressive malignancies defined by morphologic and molecular undifferentiation, and associated with core SWI/SNF deficiency. Their main differential diagnoses include high-grade endometrial and ovarian carcinomas that often show overlapping morphologic and molecular profiles. Loss of cell lineage markers expression by immunohistochemistry (IHC) is commonly used to assist diagnosis, but it has poor specificity, while core SWI/SNF deficiency is much more specific. Approximately half of SWI/SNF-deficient DDC/UDC are associated with loss of ARID1B expression, yet, unlike the other core SWI/SNF proteins (SMARCA4 and SMARCB1), this test is rarely available, even in tertiary centers. Mutational testing for ARID1B is increasingly common among targeted DNA sequencing panels, but it is difficult to interpret in the absence of IHC results. Overall, the importance of including ARID1B IHC as part of the routine panel for undifferentiated gynecologic malignancies should be emphasized, especially as SWI/SNF inactivation is becoming a necessary biomarker for diagnostics, clinical management, and clinical trial enrollment. MDPI 2023-08-24 /pmc/articles/PMC10486746/ /pubmed/37686505 http://dx.doi.org/10.3390/cancers15174229 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Opinion
Tessier-Cloutier, Basile
ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
title ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
title_full ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
title_fullStr ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
title_full_unstemmed ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
title_short ARID1B Immunohistochemistry Is an Important Test for the Diagnosis of Dedifferentiated and Undifferentiated Gynecologic Malignancies
title_sort arid1b immunohistochemistry is an important test for the diagnosis of dedifferentiated and undifferentiated gynecologic malignancies
topic Opinion
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486746/
https://www.ncbi.nlm.nih.gov/pubmed/37686505
http://dx.doi.org/10.3390/cancers15174229
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