Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Mod Pathol. 2022 Jul;35(7):946-955. doi: 10.1038/s41379-021-01001-7. Epub 2021 Dec 21.
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 are differentially expressed in WD compared to controls, and could serve as potential immunohistochemical markers for screening. Several proteins were differentially expressed in WD and immunohistochemical stains for two (metallothionein (MT) and cytochrome C oxidase copper chaperone (COX17)) were tested and compared to other methods of diagnosis in WD including copper staining and quantitative copper assays. We found diffuse metallothionein 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 (none of which showed strong, diffuse staining), 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, 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 WD that could be widely deployed as a screening tool for liver biopsies in which WD is in the clinical or histologic differential diagnosis.
威尔逊病（WD）的诊断可能很困难，因为其临床表现多种多样，但早期诊断很重要，因为有效的治疗方法是可用的，可以防止疾病进展。同样，由于组织学表现范围广泛，在肝活检标本中诊断 WD 也很困难。如果有一种可以帮助识别 WD 患者的染色剂，那将是非常有价值的。本研究的目的是使用基于质谱的蛋白质组学来鉴定 WD 与对照相比差异表达的潜在蛋白，并作为筛选的潜在免疫组织化学标志物。在 WD 中发现了几种差异表达的蛋白，并且对两种蛋白（金属硫蛋白（MT）和细胞色素 C 氧化酶铜伴侣（COX17））进行了免疫组织化学染色，并与 WD 中的其他诊断方法（铜染色和定量铜测定）进行了比较。我们发现所有 WD 患者的肝标本均有弥漫性 MT 免疫反应（n=20）；染色强度为中度至强。这种染色模式与对照组的标本明显不同（对照组无强弥漫性染色），包括可能处于 WD 的临床或组织学差异的疾病（脂肪性肝炎（n=51），慢性病毒性肝炎（n=40），自身免疫性肝炎（n=50），慢性胆道疾病（n=42）和正常肝脏（n=20））。COX17 免疫染色显示 WD 和对照组之间的表达无显着差异。MT 的诊断 WD 的敏感性高于罗丹明。虽然定量肝铜测定也具有很高的敏感性，但它们需要更多的组织，成本更高，周转时间更长，并且不如免疫组织化学染色广泛可用。我们得出结论，MT IHC 是诊断 WD 的一种敏感的免疫组织化学染色方法，可以广泛用作 WD 临床或组织学鉴别诊断的肝活检筛查工具。
