Stokes Nadarra L, Patil Ameya, Adeyi Oyedele, Bhalla Amarpreet, Brown Ian, Byrnes Kathleen, Calderaro Julien, Chen Diane, Chen Wei, Cooper Caroline, Dhall Deepti, Frankel Wendy, Gooch Gretchen Galliano, Gonzalez Raul S, Hammer Suntrea, Hale Gillian, Lagana Stephen, McKenzie Catriona, Allende Daniela S, Moreira Roger K, Nakhleh Raouf, Nalbantoglu ILKe, Pai Rish K, Salomao Marcela, Schaeffer David F, Shih Angela, Shin Joo-Shik, Simoes Camila C, Vij Mukul, Rela Mohamed, Xue Yue, Yantiss Rhonda K, Sabatto Bassel Zein, Graham Rondell P
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
Mod Pathol. 2025 Jan;38(1):100628. doi: 10.1016/j.modpat.2024.100628. Epub 2024 Oct 9.
Wilson disease (WD) is a rare autosomal recessive condition with protean clinical manifestations that result from biallelic ATP7B mutations. However, nondestructive tissue tests to be applied clinically to tissue specimens are not widely available to effectively assess patients for possible WD. Previously, we showed that metallothionein (MTH) immunohistochemistry (IHC) has a high sensitivity and specificity for WD diagnosis and, thus, represents a potentially powerful diagnostic tool that can be used in routine histologic sections. This study aimed to validate this finding in a large cohort of bona fide patients with WD and to correlate metallothionein expression with other histologic features. We identified 91 cases of WD, which included 28 needle biopsies and 64 explants from 14 centers worldwide. Histologic features were evaluated, and a histopathological pattern was assigned to each case. All cases were evaluated with Masson trichrome and MTH IHC (clone UC1MT, Abcam) using a previously published technique. Liver tissues from chronic cholestatic diseases (n = 42) were used as controls. The median age of the cohort was 28.5 years. Of the 91 total cases, 83 were positive for MTH immunostain. In the controls, all 42 cases were negative for MTH immunostain. The sensitivity and specificity of MTH immunostain for WD were 91.20% and 100%, respectively. MTH IHC is a highly sensitive and specific cost-effective screening tool for WD. It can be used for patients across age groups, varied histologic patterns, and fibrosis stages. This marker could prove to be a valuable tool in the evaluation of patients with possible WD.
威尔逊病（WD）是一种罕见的常染色体隐性疾病，具有多种临床表现，由双等位基因ATP7B突变引起。然而，临床上可应用于组织标本的非破坏性组织检测方法尚未广泛普及，无法有效评估患者是否可能患有WD。此前，我们发现金属硫蛋白（MTH）免疫组织化学（IHC）对WD诊断具有高敏感性和特异性，因此是一种可用于常规组织切片的潜在有力诊断工具。本研究旨在在一大群确诊的WD患者中验证这一发现，并将金属硫蛋白表达与其他组织学特征相关联。我们确定了91例WD病例，其中包括来自全球14个中心的28例针吸活检和64例切除组织。评估组织学特征，并为每个病例指定一种组织病理学模式。所有病例均采用先前发表的技术，用Masson三色染色法和MTH IHC（克隆UC1MT，Abcam）进行评估。将慢性胆汁淤积性疾病患者的肝组织（n = 42）用作对照。该队列的中位年龄为28.5岁。在91例病例中，83例MTH免疫染色呈阳性。在对照组中，所有42例MTH免疫染色均为阴性。MTH免疫染色对WD的敏感性和特异性分别为91.20%和100%。MTH IHC是一种用于WD的高敏感性、特异性且经济高效的筛查工具。它可用于不同年龄组、各种组织学模式和纤维化阶段的患者。该标志物可能是评估可能患有WD的患者的一种有价值的工具。
