Comparative Study of Arginase-1 (Arg-1) and Hepatocyte Paraffin Antigen (HepPar-1) Expression in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is among the most rapidly fatal malignancies worldwide. It is considered as the most commonly occurring primary liver cancer and ranks as the fifth most frequently occurring cancer worldwide. It is also considered as the third leading cause of cancer deaths all over the world. It was mentioned that the incidence of HCC has risen due to increased burden of chronic liver disease in Egypt. Metastatic tumors of the liver are reported to be more common than primary liver neoplasms and sometimes represent the initial clinical manifestations of primaries in the GI tract, breast, lung, or pancreas. Because of the wide spectrum of histologic differentiation with a great diversity of appearances of HCC, the differential diagnosis between HCC and other malignancies involving the liver can be difficult. Intrahepatic cholangio-carcinoma, metastatic tumors like renal cell carcinoma, adrenocortical tumors, carcinoid, malignant melanoma, and poorly differentiated adenocarcinoma, can closely mimic HCC and pose diagnostic problems. Immunohistochemical methods are often required to facilitate the diagnosis Variable immunohistochemical markers have been used to overcome this obstacle, and confirm the hepatocytic origin of the tumor, the most conventionally implemented is Hepatocyte paraffin antigen (HepPar-1), which was established to be a fairly sensitive marker to HCC. However, it was proved that HepPar-1 may also stain hepatoid adenocarcinomas of the gastrointestinal tract which mainly arise in the stomach. HepPar-1 may rarely also stain adrenal gland carcinomas and other biliary tract, small intestinal and gastric carcinomas. Arginase-1 (Arg-1) has been described recently as a useful and specific marker for hepatocytes and hepatocellular carcinoma. Few studies in the recent literature have emphasized the value of Arg-1 as an ancillary diagnostic tool for HCC, many of them were implemented upon cytology material. Our aim in the current work was to study the expression of Arg-1 in hepatocellular carcinoma, intrahepatic cholangiocarcinoma and metastatic tumors of the liver, and to compare its sensitivity and specificity for HCC with HepPar-1, which was chosen as the most widely used marker for hepatocytic differentiation This study included (80) cases (50: HCC, 5: intrahepatic cholangiocarcinomas and 25: metastatic liver tumors). All cases were retrieved from the archival files of the pathology labs of Ain Shams University Hospitals (from 2006-2012). Immunohistochemical study was performed using Arg-1 and HepPar-1 antibodies In this study the HCC patients’ mean age was 61.86 years, there was a male predominance among HCC patients (84%) with a male to female ratio of 4:1. 94% of HCC cases tested positive for HCV markers with only one case of HBV infection. As regards to alpha-fetoprotein serum level, we observed a high level in (76%) of studied HCC cases. Arg-1 showed higher sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy than HepPar-1. Arg-1 proved to be a sensitive marker for the whole spectrum of hepatocellular differentiation, and it represents a reliable ancillary tool for diagnosis of HCC. Its staining is diffuse in most of the studied HCCs. This highlights its valuable role in assessment of small liver biopsies. Also, Arg-1 is found to be a specific marker that can efficiently differentiate between HCC and other tumors, rendering it a promising marker to identify an origin of hepatocellular carcinoma in cases of metastases of unknown primary. Arg-1 expression; with its higher sensitivity to high grade/poorly differentiated HCCs as compared to HepPar-1, proves its superiority in distinguishing HCC from other mimics, irrespective of the degree of differentiation. However, Arg-1 has no role in differentiation between well differentiated HCC and benign hepatocellular lesions.