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
ABSTRACT 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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ABSTRACT: BACKGROUND: 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.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. RESULTS: 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%. CONCLUSION: 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 slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9991436558072434.Diagnostic Pathology 10/2012; 7(1):149. DOI:10.1186/1746-1596-7-149 · 2.41 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor seen in adults. The histopathologic diagnosis of classic or conventional differentiated HCC is seldom challenging, however, HCC is a particularly heterogenous tumor. HCC often has a medley of morphologic features that are either challenging to recognize as hepatocellular, or represents components that are of complex histogenesis. This review focuses on the heterogenous nature of HCC, with discussion of the histologic variants, some of which the clinical significance is unknown. In some cases, a lack of numbers precludes elucidating the clinical significance of these variants. Ultimately, larger studies are needed to determine the diagnostic and prognostic relevance of the phantasmagoria within HCC.Journal of clinical gastroenterology 04/2013; DOI:10.1097/MCG.0b013e318291f237 · 3.19 Impact Factor
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ABSTRACT: Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR(-/-) and SHP(-/-) mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR(-/-) mice and therefore, increased SHP expression in FXR(-/-) mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR(-/-) mice with overexpression of SHP in hepatocytes (FXR(-/-)/SHP(Tg)) and determined the contribution of SHP in HCC development in FXR(-/-) mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR(-/-) mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicators cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR(-/-) mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver.Toxicology and Applied Pharmacology 06/2013; 272(2). DOI:10.1016/j.taap.2013.06.016 · 3.63 Impact Factor