Proteomics

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Metallothionein immunohistochemistry has high sensitivity and specificity for detection of Wilson disease


ABSTRACT: Diagnosis of Wilson disease (WD) can be difficult because of its protean clinical presentation, but early diagnosis is important because effective treatment is available and can prevent disease progression. Using quantitative proteomics, we characterized proteins that are differentially expressed in WD compared to normal liver. Further the expression of MT1M and COX17 were validated using immunohistochemistry. We found diffuse MT immunoreactivity in all liver specimens from patients with WD (n=20), the intensity of the staining was moderate to strong. This staining pattern was distinct from that seen in specimens from the control groups which included diseases that may be in the clinical or histologic differential of WD (steatohepatitis (n=51), chronic viral hepatitis (n=40), autoimmune hepatitis (n=50), chronic biliary tract disease (n=42), and normal liver (n=20)). COX17 immunostain showed no significant difference in expression between the WD and control groups. MT had higher sensitivity than rhodanine for diagnosis of WD. While the quantitative liver copper assays also had high sensitivity, they require more tissue, have a higher cost, have longer turnaround time, and are less widely available than an immunohistochemical stain. We conclude that MT IHC is a sensitive immunohistochemical stain for the diagnosis of Wilson disease that could be widely deployed as a screening tool for liver biopsies in which Wilson disease is in the clinical or histologic differential diagnosis.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

DISEASE(S): Wilson Disease

SUBMITTER: Akhilesh Pandey  

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD029069 | Pride | 2023-04-18

REPOSITORIES: Pride

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Metallothionein immunohistochemistry has high sensitivity and specificity for detection of Wilson disease.

Rowan Daniel J DJ   Mangalaparthi Kiran K KK   Singh Smrita S   Moreira Roger K RK   Mounajjed Taofic T   Lamps Laura L   Westerhoff Maria M   Cheng Jerome J   Bellizzi Andrew M AM   Allende Daniela S DS   Pandey Akhilesh A   Graham Rondell P RP  

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20211221 7


Diagnosis of Wilson disease (WD) can be difficult because of its protean clinical presentations, but early diagnosis is important because effective treatment is available and can prevent disease progression. Similarly, diagnosis of WD on liver biopsy specimens is difficult due to the wide range of histologic appearances. A stain that could help identify WD patients would be of great value. The goal of this study was to use mass spectrometry-based proteomics to identify potential proteins that ar  ...[more]

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