Metallothionein: a game changer in histopathological diagnosis of Wilson disease.
Wilson disease
biomarker
immunohistochemistry
metallothionein
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
11
08
2023
received:
12
04
2023
accepted:
18
08
2023
medline:
7
11
2023
pubmed:
4
9
2023
entrez:
4
9
2023
Statut:
ppublish
Résumé
Wilson disease (WD) is a genetic disorder of copper metabolism caused by mutations in the ATP7B gene. Toxic copper accumulation leads to hepatic, neurologic, and psychiatric disorders with variable presentation. Metallothionein (MT) immunohistochemistry was proposed as a diagnostic marker. MT immunohistochemistry was performed on liver specimens of WD patients (n = 64) and control cases (n = 160) including acute liver failure, steatotic liver disease, autoimmune hepatitis, normal liver, primary biliary cholangitis, primary and secondary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. The optimal cutoff for detection of WD was determined by receiver operating characteristic (ROC) analysis. At least moderate staining in >50% of hepatocytes was observed in 81% of analysed liver specimens (n = 56/69) of WD patients, while only five control cases showed this staining pattern. The sensitivity, specificity, and accuracy for a new diagnosis of WD were 85.7%, 96.9%, and 94.9%, respectively. Sensitivity in nonfibrotic patients was 70.6% and this MT pattern was robust in small biopsies. The hepatic copper concentration was similar between MT-positive and MT-negative liver samples (P > 0.05). Zinc treatment may induce hepatocellular MT expression. Kayser-Fleischer rings (50% versus 15%) and neurologic disorders (50% versus 13%) were significantly more prevalent in MT-negative compared to MT-positive WD patients, respectively. MT immunostaining is an excellent biomarker for histological diagnosis of WD, should be incorporated in the diagnostic work-up of patients with potential WD, and is useful in a modified Leipzig score.
Substances chimiques
Copper
789U1901C5
Metallothionein
9038-94-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
936-948Informations de copyright
© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.
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