Immunohistochemical distinction of hepatocellular carcinoma using Arginase-1, Hepatocyte paraffin antigen -1 and Glypican-3

Abstract

The distinction of hepatocellular carcinoma (HCC) from the metastatic carcinoma and cholangiocarcinoma in the liver often presents a diagnostic challenge that carries significant impact on its subsequent management. We aimed to investigate the expressions of arginase-1, hepatocyte paraffin antigen -1 (HepPar-1), and glypican-3 (GPC-3) in a trial to distinguish HCC from non-hepatocellular carcinomas involving the liver.The study included 69 cases, with 32 HCC, 28 MC, 4 CC and 5 normal liver tissues. The predictive capacity of arginase-1, HepPar-1 and GPC-3 staining was determined using sensitivity, specificity, positive predictive value, and negative predictive value calculations.Both arginase-1 and HepPar-1 expressions were present in all cases of nonmalignant 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. In contrast, GPC-3 immunoreactivity was detected in 2 of 28 (7.1%) cases 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%.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 can aid in precise diagnosis of HCC and distinguishing it from non-hepatocellular carcinomas.