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ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previo...

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Autores principales: Sala, Margaux, Gonzales, Delphine, Leste‐Lasserre, Thierry, Dugot‐Senant, Nathalie, Paradis, Valérie, Di Tommaso, Sylvaine, Dupuy, Jean‐William, Pitard, Vincent, Dourthe, Cyril, Sciarra, Amedeo, Sempoux, Christine, Ferrell, Linda D., Clouston, Andrew D., Miller, Gregory, Yeh, Mathew M., Thung, Swan, Gouw, Annette S.H., Quaglia, Alberto, Han, Jing, Huan, Ji, Fan, Cathy, Crawford, James, Nakanuma, Yasuni, Harada, Kenichi, le Bail, Brigitte, Castain, Claire, Frulio, Nora, Trillaud, Hervé, Possenti, Laurent, Blanc, Jean‐Frédéric, Chiche, Laurence, Laurent, Christophe, Balabaud, Charles, Bioulac‐Sage, Paulette, Raymond, Anne Aurélie, Saltel, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262286/
https://www.ncbi.nlm.nih.gov/pubmed/32490318
http://dx.doi.org/10.1002/hep4.1514
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author Sala, Margaux
Gonzales, Delphine
Leste‐Lasserre, Thierry
Dugot‐Senant, Nathalie
Paradis, Valérie
Di Tommaso, Sylvaine
Dupuy, Jean‐William
Pitard, Vincent
Dourthe, Cyril
Sciarra, Amedeo
Sempoux, Christine
Ferrell, Linda D.
Clouston, Andrew D.
Miller, Gregory
Yeh, Mathew M.
Thung, Swan
Gouw, Annette S.H.
Quaglia, Alberto
Han, Jing
Huan, Ji
Fan, Cathy
Crawford, James
Nakanuma, Yasuni
Harada, Kenichi
le Bail, Brigitte
Castain, Claire
Frulio, Nora
Trillaud, Hervé
Possenti, Laurent
Blanc, Jean‐Frédéric
Chiche, Laurence
Laurent, Christophe
Balabaud, Charles
Bioulac‐Sage, Paulette
Raymond, Anne Aurélie
Saltel, Frédéric
author_facet Sala, Margaux
Gonzales, Delphine
Leste‐Lasserre, Thierry
Dugot‐Senant, Nathalie
Paradis, Valérie
Di Tommaso, Sylvaine
Dupuy, Jean‐William
Pitard, Vincent
Dourthe, Cyril
Sciarra, Amedeo
Sempoux, Christine
Ferrell, Linda D.
Clouston, Andrew D.
Miller, Gregory
Yeh, Mathew M.
Thung, Swan
Gouw, Annette S.H.
Quaglia, Alberto
Han, Jing
Huan, Ji
Fan, Cathy
Crawford, James
Nakanuma, Yasuni
Harada, Kenichi
le Bail, Brigitte
Castain, Claire
Frulio, Nora
Trillaud, Hervé
Possenti, Laurent
Blanc, Jean‐Frédéric
Chiche, Laurence
Laurent, Christophe
Balabaud, Charles
Bioulac‐Sage, Paulette
Raymond, Anne Aurélie
Saltel, Frédéric
author_sort Sala, Margaux
collection PubMed
description Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico‐pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis.
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spelling pubmed-72622862020-06-01 ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice Sala, Margaux Gonzales, Delphine Leste‐Lasserre, Thierry Dugot‐Senant, Nathalie Paradis, Valérie Di Tommaso, Sylvaine Dupuy, Jean‐William Pitard, Vincent Dourthe, Cyril Sciarra, Amedeo Sempoux, Christine Ferrell, Linda D. Clouston, Andrew D. Miller, Gregory Yeh, Mathew M. Thung, Swan Gouw, Annette S.H. Quaglia, Alberto Han, Jing Huan, Ji Fan, Cathy Crawford, James Nakanuma, Yasuni Harada, Kenichi le Bail, Brigitte Castain, Claire Frulio, Nora Trillaud, Hervé Possenti, Laurent Blanc, Jean‐Frédéric Chiche, Laurence Laurent, Christophe Balabaud, Charles Bioulac‐Sage, Paulette Raymond, Anne Aurélie Saltel, Frédéric Hepatol Commun Original Articles Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico‐pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis. John Wiley and Sons Inc. 2020-04-11 /pmc/articles/PMC7262286/ /pubmed/32490318 http://dx.doi.org/10.1002/hep4.1514 Text en © 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Sala, Margaux
Gonzales, Delphine
Leste‐Lasserre, Thierry
Dugot‐Senant, Nathalie
Paradis, Valérie
Di Tommaso, Sylvaine
Dupuy, Jean‐William
Pitard, Vincent
Dourthe, Cyril
Sciarra, Amedeo
Sempoux, Christine
Ferrell, Linda D.
Clouston, Andrew D.
Miller, Gregory
Yeh, Mathew M.
Thung, Swan
Gouw, Annette S.H.
Quaglia, Alberto
Han, Jing
Huan, Ji
Fan, Cathy
Crawford, James
Nakanuma, Yasuni
Harada, Kenichi
le Bail, Brigitte
Castain, Claire
Frulio, Nora
Trillaud, Hervé
Possenti, Laurent
Blanc, Jean‐Frédéric
Chiche, Laurence
Laurent, Christophe
Balabaud, Charles
Bioulac‐Sage, Paulette
Raymond, Anne Aurélie
Saltel, Frédéric
ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
title ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
title_full ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
title_fullStr ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
title_full_unstemmed ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
title_short ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
title_sort ass1 overexpression: a hallmark of sonic hedgehog hepatocellular adenomas; recommendations for clinical practice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262286/
https://www.ncbi.nlm.nih.gov/pubmed/32490318
http://dx.doi.org/10.1002/hep4.1514
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