ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
Hepatol Commun. 2020-04-11; 4(6): 809-824
DOI: 10.1002/hep4.1514
Read on PubMed
Sala M(1), Gonzales D(2), Leste-Lasserre T(2), Dugot-Senant N(3), Paradis V(4), Di Tommaso S(1)(5), Dupuy JW(6), Pitard V(7), Dourthe C(1)(5), Sciarra A(8), Sempoux C(8), Ferrell LD(9), Clouston AD(10), Miller G(10), Yeh MM(11), Thung S(12), Gouw ASH(13), Quaglia A(14), Han J(15), Huan J(15), Fan C(16), Crawford J(16), Nakanuma Y(17), Harada K(18), le Bail B(1)(19), Castain C(19), Frulio
N(20), Trillaud H(20)(21), Possenti L(22), Blanc JF(1)(22), Chiche L(23), Laurent C(23), Balabaud C(1), Bioulac-Sage P(1), Raymond AA(1)(5), Saltel F(1)(5).
Author information:
(1)BaRITOn Bordeaux Research in Translational Oncology University of Bordeaux INSERM UMR1053 Bordeaux France.
(2)Neurocentre Magendie INSERM U1215 Bordeaux France.
(3)Plateforme d’histopathologie, TBM-Core US 005 Bordeaux France.
(4)INSERM; APHP, Pathology Department Beaujon Hospital Université de Paris Hopital Beaujon Clichy France.
(5)Plateforme Oncoprot TBM-Core US 005 Bordeaux France.
(6)Plateforme Protéome Centre de Génomique Fonctionnelle University of Bordeaux Bordeaux France.
(7)ImmunoConcept CNRS UMR 5164 University of Bordeaux Bordeaux France.
(8)Service of Clinical Pathology Institute of Pathology Lausanne University Hospital University of Lausanne Lausanne Switzerland.
(9)Department of Pathology University of California San Francisco CA.
(10)Centre for Liver Disease Research School of Medicine University of Queensland Brisbane QLD Australia.
(11)University of Washington School of Medicine Seattle WA.
(12)Icahn School of Medicine at Mount Sinai New York NY.
(13)Department of Pathology University of Groningen University Medical Center Groningen Groningen the Netherlands.
(14)Department of Cellular Pathology Royal Free London NHS Foundation Trust London United Kingdom.
(15)Department of Pathology Zhongshan Hospital Fudan University Shanghai China.
(16)Department of Pathology and Laboratory Medicine Hofstra/Northwell Hempstead NY.
(17)Pathology Division Shizuoka Cancer Center Sunto-gun Japan.
(18)Department of Human Pathology Kanazawa University Graduate School of Medical Sciences Kanazawa Japan.
(19)Department of Pathology CHU Bordeaux Bordeaux France.
(20)Department of Diagnostic and Interventional Radiology CHU Bordeaux Bordeaux France.
(21)EA Imotion University of Bordeaux Bordeaux France.
(22)Department of Hepatology and Oncology INSERM CIC1401 CHU Bordeaux Bordeaux France.
(23)Department of Digestive Surgery CHU Bordeaux Bordeaux France.
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.
© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.