Cargando…

Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry

The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been...

Descripción completa

Detalles Bibliográficos
Autores principales: Aguilar, Mitzi, Chen, Hao, Rivera-Colon, Glorimar, Niu, Shuang, Carrick, Kelley, Gwin, Katja, Cuevas, Ileana C., Sahoo, Subhransu S., Li, Hao-Dong, Zhang, Song, Zheng, Wenxin, Lucas, Elena, Castrillon, Diego H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860214/
https://www.ncbi.nlm.nih.gov/pubmed/34545858
http://dx.doi.org/10.1097/PAS.0000000000001810
_version_ 1784654621346627584
author Aguilar, Mitzi
Chen, Hao
Rivera-Colon, Glorimar
Niu, Shuang
Carrick, Kelley
Gwin, Katja
Cuevas, Ileana C.
Sahoo, Subhransu S.
Li, Hao-Dong
Zhang, Song
Zheng, Wenxin
Lucas, Elena
Castrillon, Diego H.
author_facet Aguilar, Mitzi
Chen, Hao
Rivera-Colon, Glorimar
Niu, Shuang
Carrick, Kelley
Gwin, Katja
Cuevas, Ileana C.
Sahoo, Subhransu S.
Li, Hao-Dong
Zhang, Song
Zheng, Wenxin
Lucas, Elena
Castrillon, Diego H.
author_sort Aguilar, Mitzi
collection PubMed
description The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually—and more importantly as a group—has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN.
format Online
Article
Text
id pubmed-8860214
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-88602142022-02-24 Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry Aguilar, Mitzi Chen, Hao Rivera-Colon, Glorimar Niu, Shuang Carrick, Kelley Gwin, Katja Cuevas, Ileana C. Sahoo, Subhransu S. Li, Hao-Dong Zhang, Song Zheng, Wenxin Lucas, Elena Castrillon, Diego H. Am J Surg Pathol Original Articles The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually—and more importantly as a group—has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN. Lippincott Williams & Wilkins 2022-03 2021-09-17 /pmc/articles/PMC8860214/ /pubmed/34545858 http://dx.doi.org/10.1097/PAS.0000000000001810 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Articles
Aguilar, Mitzi
Chen, Hao
Rivera-Colon, Glorimar
Niu, Shuang
Carrick, Kelley
Gwin, Katja
Cuevas, Ileana C.
Sahoo, Subhransu S.
Li, Hao-Dong
Zhang, Song
Zheng, Wenxin
Lucas, Elena
Castrillon, Diego H.
Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
title Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
title_full Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
title_fullStr Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
title_full_unstemmed Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
title_short Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
title_sort reliable identification of endometrial precancers through combined pax2, β-catenin, and pten immunohistochemistry
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860214/
https://www.ncbi.nlm.nih.gov/pubmed/34545858
http://dx.doi.org/10.1097/PAS.0000000000001810
work_keys_str_mv AT aguilarmitzi reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT chenhao reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT riveracolonglorimar reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT niushuang reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT carrickkelley reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT gwinkatja reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT cuevasileanac reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT sahoosubhransus reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT lihaodong reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT zhangsong reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT zhengwenxin reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT lucaselena reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry
AT castrillondiegoh reliableidentificationofendometrialprecancersthroughcombinedpax2bcateninandptenimmunohistochemistry