The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1

Abstract

BackgroundThe ability to distinguish hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) involving the liver and cholangiocarcinoma (CC) by immunohistochemistry has been limited by the lack of a reliable positive marker for hepatocellular differentiation. Arginase-1 is a marker for HCC recently described in some literature.AimTo examine the immunohistochemical staining of arginase-1 in cases of HCC, MC involving the liver and CC as compared to hepatocyte paraffin antigen -1 (HepPar-1) in an attempt to further define the diagnostic utility of arginase-1 in differentiating these tumors.Materials and methodsA comparative immunohistochemical study of arginase-1 and HepPar-1expression was performed in 50 HCC cases, 38 cases of MC to the liver from varying sites, 12 cases of CC and 10 specimens of normal liver tissues. The predictive capacity of arginase-1 and HepPar-1 staining was determined using sensitivity, specificity, positive predictive value, and negative predictive value calculations.ResultsAll normal liver tissues (no=10), non- neoplastic cirrhotic liver tissues adjacent to HCC (no=42) as well as those adjacent to MC (no= 9) showed diffuse and strong immunostaining for both arginase-1 and HepPar-1. Arginase-1 demonstrated positive immunoreactivity in 42 of 50 (84%) cases of HCC compared with 35 of 50 (70%) for HepPar-1. Only one of 38 (2.6%) cases of MC and one of 12 (8.3%) cases of CC showed positive immunoreactivity for arginase-1. In contrast, HepPar-1 immunoreactivity was detected in 6 of 38 (15.8%) cases of MC and in 2 of 12 (16.7%) cases of CC. Arginase -1 showed a significantly higher sensitivity for HCC diagnosis (84%) compared to HepPar -1(70%) (p=0.016). The specificity of arginase-1 for HCC diagnosis was higher (96%) than that of HepPar -1 (84%); nevertheless, this was not statistically significant (p=0.109). Howerver, the combination of both immunomarkers for the diagnosis of HCC, raised the specificity to 100%.ConclusionArginase-1 immunostaining has a higher sensitivity and specificity than HepPar-1 for HCC diagnosis. Furthermore, the combined use of arginase-1 and HepPar-1 can provide a potentially promising tool to improve the accuracy in distinguishing HCC from metastatic carcinoma and cholangiocarcinoma.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9991436558072434.

Comparison of 5 Immunohistochemical Markers of Hepatocellular Differentiation for the Diagnosis of Hepatocellular Carcinoma

“…Similar to our finding of 98% sensitivity, figures ranging from 84% to 96% have been reported. 13,14,18 The high sensitivity of Arg-1 (81%-84%) has also been observed in cytology material. 19,20 The high sensitivity of Arg-1 was also observed in poorly differentiated HCC (95% in our study, which is similar to the 90% reported by Yan et al 13 ) as well as in scirrhous HCC.…”

“…Initial studies have shown that Arg-1 is a highly sensitive and specific marker for hepatocellular differentiation. [12][13][14] Bile salt export pump (BSEP) is a liver-specific ATPbinding cassette transporter encoded by the ABCB11 gene, which is expressed exclusively in the liver canalicular membrane and involved with bile acid transport. 15 The BSEP marker has been shown to be specific and sensitive for hepatocellular differentiation, but its diagnostic utility in HCC has not been explored in detail.…”

Current concepts in the immunohistochemical evaluation of liver tumors

“…Developed in 1993 from a failed liver allograft [36] , this antibody has been found to be relatively sensitive (70%, although some authors report higher sensitivity) and specific (84%) for hepatocellular differentiation [41] , in both normal tissue and HCC, as well as hepatoblastoma. Caveats with this marker include the reported loss of sensitivity as tumors become less differentiated [36,42,43] , and frequent negativity in the scirrhous variant [44] .…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…Indeed, subsequent studies have confirmed that Arg-1 is currently the best available hepatocellular marker, with a sensitivity around 90%. [104][105][106] In comparison with Hep Par 1, Arg-1 is much less frequently positive in adenocarcinomas. [103][104][105][106][107] Like Hep Par 1, positive Arg-1 staining can also be patchy.…”