Arginase‐1: A novel immunohistochemical marker of hepatocellular differentiation in fine needle aspiration cytology

Abstract

Arginase-I is a key urea cycle metalloenzyme that has been used as an immunohistochemistry (IHC) marker for hepatocellular carcinoma (HCC). Previous studies have demonstrated the efficacy of HepPar-1 and glypican-3 (GPC-3) IHC in liver fine needle aspiration (FNA) cytology. Arginase-1 IHC was performed on FNA cell blocks, and its performance characteristics were compared with HepPar-1 and GPC-3. Ninety-two formalin-fixed, paraffin-embedded cell blocks were selected (HCC [n = 44], cirrhosis [n = 2], focal nodular hyperplasia [n = 3], hepatic adenomas [n = 2], dysplastic nodules [n = 6], and metastatic carcinomas [n = 35]). IHC staining with antibodies directed against arginase-1, HepPar-1, and GPC-3 was performed with appropriate positive and negative controls. Arginase-1 positivity was demonstrated in 37 of 44 (84.1%) cases of HCC, compared with 32 of 44 cases (72.7%) and 25 of 44 cases (56.8%) for HepPar-1 and GPC-3, respectively. Arginase-1 and GPC-3 expression were not observed in any cases of metastatic carcinoma (0%), whereas HepPar-1 expression was present in 1 case of metastatic carcinoma. In addition, both arginase-1 and HepPar-1 expression were present in all 13 cases (100%) of nonmalignant hepatocellular lesions, whereas GPC-3 expression was absent in all 13 cases (0%). This study demonstrates that both arginase-1 and HepPar-1 are effective IHC markers of hepatocellular differentiation. Furthermore, arginase-1 demonstrates superior sensitivity compared with GPC-3 and HepPar-1 in the diagnosis of HCC, whereas GPC-3 demonstrates superior specificity, as staining is not observed in benign hepatocellular lesions. Hence, use of arginase-1 with HepPar-1 and GPC-3 can aid in the diagnosis of HCC and separating from metastatic carcinoma.