of MC and negative in all cases of CC. Arginase-1 was more sensitive (87.5%) than HepPar-1 (71.9%) or GPC-3 (65.6%) for HCC. GPC-3 was more specific (93.8%) than HepPar-1 (87.5%) and arginase-1 (90.6%). However, the combination of the three biomarkers for the diagnosis of HCC raised the specificity to 100%. CONCLUSION: Arginase-1 and HepPar-1 are effective biomarkers for HCC differentiation. Also, arginase-1 demonstrates a superior sensitivity in comparison with GPC-3 and HepPar-1 in the diagnosis of HCC, whereas GPC-3 demonstrates superior specificity. Hence, the use of combination of arginase-1 with HepPar-1 and GPC-3 could be useful in the precise diagnosis of HCC and distinguishing it from non-HCC.
INTRODUCTIONHepatocellular Carcinoma (HCC) is the most common primary cancer of liver, representing the third most common cause of cancer deaths all over the world [1] . Egypt has a high prevalence of HCC; it is the second most cancer site among males after cancer bladder and seventh among females [2] . Such high incidence has been attributed to the high prevalence of hepatitis C virus (HCV) amongst Egyptians [3] .Based on histological characters, most HCCs can be easily identified on hematoxylin and eosin stained sections. However, some types of benign and malignant tumors may share the morphologic features. HCC mimickers include some cases of adrenocortical carcinoma, renal cell carcinoma (RCC), large cell neuroendocrine carcinoma, clear cell sarcoma, melanoma and angiomyolipoma [4,5] . In ABSTRACT AIM: The distinction of hepatocellular carcinoma (HCC) from the metastatic carcinoma (MC) and intrahepatic cholangiocarcinoma (CC) often presents a diagnostic challenge that carries a significant impact on its subsequent management. In this study we aimed to evaluate the immunohistochemical expressions of arginase-1, hepatocyte paraffin antigen-1 (HepPar-1), and glypican-3 (GPC-3) in a trial to distinguish HCC from non-HCC involving the liver.
MATERIALS AND METHODS:The study included 64 cases (32 HCC, 28 MC and 4 CC) and 5 specimens of normal liver tissues. These cases were investigated retrospectively from the archive of the Pathology Department, Zagazig University Hospitals. The predictive capacity of arginase-1, HepPar-1 and GPC-3 staining was determined using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) calculations. RESULTS: Both arginase-1 and HepPar-1 expressions were present in all cases of non-neoplastic hepatocellular tissues, whereas GPC-3 expression was absent in all cases. Only two of 28 (7.1%) cases of MC and one of 4 (25%) cases of CC showed positive immunoreactivity for arginase-1. HepPar-1 immunoreactivity was detected in 3 of 28 (10.7%) cases of MC and in one of 4 (25%) cases of CC. GPC-3 immunoreactivity was detected in 2 of 28 (7.1%) cases