Arginase-1, HepPar-1, and Glypican-3 Are the Most Effective Panel of Markers in Distinguishing Hepatocellular Carcinoma From Metastatic Tumor on Fine-Needle Aspiration Specimens

Geisinger Medical Center, Danville, PA 17822, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 08/2012; 138(2):203-10. DOI: 10.1309/AJCPK1ZC9WNHCCMU
Source: PubMed


Distinction of liver metastases from hepatocellular carcinoma (HCC) may present a diagnostic challenge. Arginase-1 (Arg-1) is a marker for HCC recently described in some literature. Immunohistochemical evaluation of Arg-1, hepatocyte paraffin-1 (HepPar-1), and glypican-3 expression was performed on 1,240 surgical specimens and 62 liver fine-needle aspiration specimens (29 HCCs, 28 metastatic tumors, and 5 benign liver cases). The staining results on tissue microarray sections showed that 2.7% and 3.1% of nonhepatic tumor cases were positive for HepPar-1 and glypican-3, respectively; none was positive for Arg-1. For fine-needle aspiration specimens, 19 HCCs were positive for all 3 markers; 9 were positive for 1 or 2 markers; and only 1 case was negative for all 3 markers. These data demonstrate that Arg-1 is the most specific marker in differentiating a non-HCC from HCC. It is recommended to use 3 markers as a panel in distinguishing HCC from metastatic carcinoma.

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Available from: Haiyan Liu, Nov 16, 2015
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    • "Our experiment indicated that anti-CPS1 antibody was more appropriate for identification of HCC CTCs than Hep Par 1 (data not shown). However, several authors reported the heterogeneous expression of CPS1 in human HCC by using CPS1 antibody or Hep Par 1 [30], [31]. It means that staining with CPS1 antibody alone may miss some HCC CTCs that lack expression of CPS1. "
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    ABSTRACT: Asialoglycoprotein receptor (ASGPR)-ligand-based separation combined with identification with Hep Par 1 or pan-cytokeratin (P-CK) antibody have been demonstrated to detect circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC). The aim of this study was to develop an improved enrichment and identification system that allows the detection of all types of HCC CTCs. The specificity of the prepared anti-ASGPR monoclonal antibody was characterized. HCC cells were bound by ASGPR antibody and subsequently magnetically isolated by second antibody-coated magnetic beads. Isolated HCC cells were identified by immunofluorescence staining using a combination of anti-P-CK and anti-carbamoyl phosphate synthetase 1 (CPS1) antibodies. Blood samples spiked with HepG2 cells were used to determine recovery and sensitivity. CTCs were detected in blood samples from HCC patients and other patients. ASGPR was exclusively expressed in human hepatoma cell line, normal hepatocytes and HCC cells in tissue specimens detected by the ASGPR antibody staining. More HCC cells could be identified by the antibody cocktail for CPS1 and P-CK compared with a single antibody. The current approach obtained a higher recovery rate of HepG2 cells and more CTC detection from HCC patients than the previous method. Using the current method CTCs were detected in 89% of HCC patients and no CTCs were found in the other test subjects. Our anti-ASGPR antibody could be used for specific and efficient HCC CTC enrichment, and anti-P-CK combined with anti-CPS1 antibodies is superior to identification with one antibody alone in the sensitivity for HCC CTC detection.
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    • "The lower diagnostic sensitivity in our study as compared to that of Yan et al. [6] may be because of the smaller sample size. In contrast, Timek et al. [25] failed to demonstrate a better sensitivity of arginase-1 for higher–grade HCC compared with HepPar-1 and they explained that by the small sampling of the cytologic specimens in the moderately to poorly differentiated HCC category (n =7), limited amount of sample for each case, and patchy/focal staining for arginase-1 in higher-grade HCC. "
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    ABSTRACT: The 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. To 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 methods A 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. All 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%. Arginase-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 slides The virtual slide(s) for this article can be found here:
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