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

Authors :
Margaux Sala
Delphine Gonzales
Thierry Leste‐Lasserre
Nathalie Dugot‐Senant
Valérie Paradis
Sylvaine Di Tommaso
Jean‐William Dupuy
Vincent Pitard
Cyril Dourthe
Amedeo Sciarra
Christine Sempoux
Linda D. Ferrell
Andrew D. Clouston
Gregory Miller
Mathew M. Yeh
Swan Thung
Annette S.H. Gouw
Alberto Quaglia
Jing Han
Ji Huan
Cathy Fan
James Crawford
Yasuni Nakanuma
Kenichi Harada
Brigitte leBail
Claire Castain
Nora Frulio
Hervé Trillaud
Laurent Possenti
Jean‐Frédéric Blanc
Laurence Chiche
Christophe Laurent
Charles Balabaud
Paulette Bioulac‐Sage
Anne Aurélie Raymond
Frédéric Saltel
Source :
Hepatology Communications, Vol 4, Iss 6, Pp 809-824 (2020)
Publication Year :
2020
Publisher :
Wolters Kluwer Health/LWW, 2020.

Abstract

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.

Details

Language :
English
ISSN :
2471254X
Volume :
4
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Hepatology Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.964102491fb4c51a8bbff73d7a74e81
Document Type :
article
Full Text :
https://doi.org/10.1002/hep4.1514