Arginase-1: a new immunohistochemical marker of hepatocytes and hepatocellular neoplasms.
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.
Yan
Benjamin C
BC
Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, USA.
Gong
Can
C
Song
Jie
J
Krausz
Thomas
T
Tretiakova
Maria
M
Hyjek
Elizabeth
E
Al-Ahmadie
Hikmat
H
Alves
Venancio
V
Xiao
Shu-Yuan
SY
Anders
Robert A
RA
Hart
John A
JA
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
D014408:Biomarkers, Tumor; D001119:Arginase