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19 Thus, it is not surprising that a subset of the pancreatic adenocarcinomas included in our analysis demonstrated arginase-1 immunoreactivity. In their tissue microarray analysis of 542 nonhepatocellular carcinomas, Yan et al demonstrated arginase-1 immunoreactivity in only 2 tumors, 1 intrahepatic cholangiocarcinoma and 1 prostatic adenocarcinoma.18 buy GSK3235025 Importantly, Yan et al did not include pancreatic adenocarcinomas in their analysis. Both HepPar-1 and glypican-3 lacked immunoreactivity in pancreatic adenocarcinomas in our analysis. HepPar-1 was positive in pulmonary, prostatic, and gastric adenocarcinomas in our analysis, all of which were negative for arginase-1 and glypican-3. Glypican-3 demonstrated moderate to diffuse staining in breast carcinomas in our analysis, whereas arginase-1 Selleck STA-9090 and HepPar-1 were typically negative or only focally positive in breast carcinomas. Our analysis of the various immunohistochemical marker combinations suggests that the combination of any positive arginase-1 staining or any positive HepPar-1 staining offers the best sensitivity (81%) and specificity (85%). The inclusion of glypican-3 in this panel only marginally increased sensitivity to 84% but reduced specificity to <80%. In addition, in our analysis, there were no hepatocellular carcinomas that demonstrated glypican-3 immunoreactivity but lacked arginase-1�Cpositive staining. Thus, the addition of glypican-3 to the immunohistochemical panel of HepPar-1 and arginase-1 does not appear to be useful. MOC-31, an antibody directed against the extracellular domain of epithelial cell adhesion molecule, has also been shown to be helpful in distinguishing hepatocellular carcinoma from adenocarcinoma.8, 22-25 Most metastatic adenocarcinomas of the liver are positive for MOC-31, whereas only rare cases of hepatocellular carcinoma demonstrated MOC-31 immunoreactivity.8, 26 The inclusion of arginase-1 and HepPar-1 as positive markers for hepatic differentiation along with MOC-31 as a positive marker for adenocarcinoma would likely be most optimal for distinguishing hepatocellular carcinoma from adenocarcinoma. This panel of immunohistochemical markers may also be useful in highlighting Histamine H2 receptor the glandular and hepatic components of combined hepatocellular carcinoma-cholangiocarcinoma. In summary, our results confirm that arginase-1 is a highly sensitive marker of hepatic differentiation and demonstrate that arginase-1 can be easily applied and interpreted in fine-needle aspiration biopsies. However, arginase-1 is not entirely specific, as diffuse, strong staining can be observed in metastatic adenocarcinoma, particularly from the pancreas. Used together, arginase-1 and HepPar-1 offer the best combined sensitivity and specificity for hepatic differentiation in fine-needle aspiration biopsies. No specific funding was disclosed. CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures. ""LUIJKX K.G. & SCHOLS J.M.G.A.
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