Arginase-1, a New Immunohistochemical Marker of Hepatocytes and Hepatocellular Neoplasms
BC Yan, C Gong, J Hart. University of Chicago Medical Center, Chicago, IL
Background: The distinction of hepatocellular carcinomas (HCCs) from metastatic tumors to the liver often presents a diagnostic challenge that carries significant impact on subsequent prognostication and therapeutic management. The number of immunohistochemical markers for pathologic identification of hepatocytes remains limited to HepPar-1, polyclonal CEA and CD10, with alpha-fetoprotein and glypican-3 labeling HCCs. The HepPar-1 antigen was recently shown to correspond to the urea cycle enzyme carbamoyl phosphate synthetase [Butler SL, Dong H, Cardona D, Jia M, Zheng R, Zhu H, Crawford JM and Liu C. (2008) Lab. Invest. 88: 78-88]. Previous immunohistochemical studies have established that arginase-1 (ARG1), another enzyme involved in the urea cycle, is also expressed in normal human liver with a high degree of specificity [Multhaupt H, Fritz P and Schumacher K. (1987) Histochemistry 87: 465-470].
Design: We examined the expression of ARG1 in 24 HCCs, 15 macroregenerative nodules (MRNs), 3 dysplastic nodules (DNs), 4 intrahepatic cholangiocarcinomas, 23 breast carcinomas, 15 pulmonary adenocarcinomas, 15 prostate carcinomas, 99 colonic adenocarcinomas and 111 salivary gland tumors by immunohistochemistry using a commercially available antibody (Sigma Aldrich) and heat retrieval methods for antigen unmasking to determine its viability as a hepatocellular marker.
Results: We found that ARG1 demonstrated strong, diffuse, nuclear and cytoplasmic expression in both normal hepatocytes and hepatocellular neoplasms: 23 of 24 HCCs (95%) exhibited strong, diffuse immunoreactivity for ARG1. All examined MRNs and DNs showed similar reactivity. In contrast, biliary epithelium, endothelial cells and Kupffer cells were non-reactive. A single combined HCC-cholangiocarcinoma exhibited ARG1 positivity only in the HCC component. In addition, one prostatic adenocarcinoma was also reactive. All other tumors examined were non-reactive.
Conclusions: ARG1 appears to be a specific marker of hepatocytes and, as such, can be used to distinguish hepatocellular carcinomas from metastatic tumors in the liver. The identification of ARG1 as a specific immunohistochemical marker of hepatocytes may lead to its development as a useful diagnostic adjunct in routine surgical pathology practice.
Category: Liver & Pancreas
Monday, March 22, 2010 1:00 PM
Poster Session II # 193, Monday Afternoon