title: Arginase-1: a new immunohistochemical marker of hepatocytes and hepatocellular neoplasms.
abstract: The distinction of hepatocellular carcinoma (HCC) from metastatic tumor in the liver often presents a diagnostic challenge that carries significant impact on prognostication and therapy. The number of diagnostically useful immunohistochemical markers of hepatocytes is limited to hepatocyte paraffin antigen (HepPar-1), polyclonal carcinoembryonic antigen, and CD10, with alpha-fetoprotein and glypican-3 labeling HCCs. Arginase-1 (Arg-1) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of arginine to ornithine and urea. We used immunohistochemistry to compare the sensitivity of Arg-1 to that of HepPar-1 in 151 HCCs. We found that the overall sensitivities of Arg-1 and HepPar-1 are 96.0% and 84.1%, respectively. The sensitivities of Arg-1 in well, moderately, and poorly differentiated HCCs are 100%, 96.2%, and 85.7%, respectively, whereas, in comparison, HepPar-1 demonstrated sensitivities of 100%, 83.0%, and 46.4% for well, moderately, and poorly differentiated tumors, respectively. There were no HCCs in our study that were reactive for HepPar-1 but nonreactive for Arg-1. We also examined Arg-1 expression in nonhepatocellular tumors, including many that are potential mimics of HCC (renal cell carcinomas, neuroendocrine tumors, melanomas, gastric adenocarcinomas, and adrenocortical carcinomas) and found that only 2 non-HCC tumors were reactive for Arg-1. Arg-1 represents a sensitive and specific marker of benign and malignant hepatocytes that may ultimately prove to be a useful diagnostic tool in routine surgical pathology practice.
authors.affiliation: Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Yan
authors.forename: Can
authors.initials: C
authors.lastname: Gong
authors.forename: Jie
authors.initials: J
authors.lastname: Song
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Maria
authors.initials: M
authors.lastname: Tretiakova
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hyjek
authors.forename: Hikmat
authors.initials: H
authors.lastname: Al-Ahmadie
authors.forename: Venancio
authors.initials: V
authors.lastname: Alves
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Xiao
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.forename: John A
authors.initials: JA
authors.lastname: Hart
mesh_terms: D001119:Arginase / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001938:Brazil; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D001119:Arginase