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: 3.01). 08/2012; 138(2):203-10. DOI: 10.1309/AJCPK1ZC9WNHCCMU
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context .- Diagnosis of primary gastrointestinal and liver neoplasms is usually straightforward. Immunohistochemistry is most helpful to differentiate metastatic carcinomas with morphologic similarity and to resolve tumors of unknown origin. Recently, several new markers highly sensitive and specific for primary liver and gastrointestinal tumors have been discovered. Their potential diagnostic application has not been widely appreciated by general practicing pathologists. In addition, a new trend in immunohistochemistry application has started, focusing on assessing predictive markers (such as human epidermal growth factor receptor 2) and mutation-specific markers (v-raf murine sarcoma viral oncogene homolog B V600E) to directly guide clinical management. Practicing pathologists need to be aware of and prepared for this evolving trend. Objectives .- To summarize the usefulness of several recently discovered immunohistochemical markers in the study of gastrointestinal and liver tumors; to suggest the most current and effective immunohistochemical panels addressing common diagnostic challenges for these tumors; to share practical experience and useful tips for human epidermal growth factor receptor 2 testing in gastric and gastroesophageal junction adenocarcinoma and v-raf murine sarcoma viral oncogene homolog B V600E immunohistochemistry in colorectal carcinoma. Data Sources .- Sources include literature review, and authors' research data and practice experience. The cases illustrated are selected from the pathology archives of the Geisinger Medical Center (Danville, Pennsylvania). Conclusions .- Application of immunohistochemistry in gastrointestinal and liver tumors continues to evolve. New tumor-specific markers constantly emerge and help pathologists to further improve diagnostic accuracy. Assessment of predictive and prognostic markers by immunohistochemistry in routine pathologic diagnosis is a new trend and will greatly facilitate the advancement of personalized cancer therapy.
    Archives of pathology & laboratory medicine 01/2015; 139(1):14-23. DOI:10.5858/arpa.2014-0153-RA · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Arginase-1 is an enzyme that catalyzes the hydrolysis of arginine to ornithine and urea in the urea cycle. In normal tissues, arginase-1 is primarily expressed in hepatocytes. Recent investigations have reported that the vast majority of hepatocellular carcinomas express this marker, but it is found only rarely in nonhepatocellular tumors. Owing to its restricted expression in hepatocellular carcinomas, arginase-1 has proved to be a useful immunohistochemical marker for assisting in distinguishing between these tumors and other neoplasms with which they may be confused.
    Advances in Anatomic Pathology 07/2014; 21(4):285-290. DOI:10.1097/PAP.0000000000000022 · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Albumin, widely recognized as a highly sensitive and specific marker of hepatocellular carcinoma (HCC), is currently unavailable in the diagnostic laboratory because of the lack of a robust platform. In a prior study we detected albumin mRNA in the majority of intrahepatic cholangiocarcinomas using a novel branched chain RNA in situ hybridization (ISH) platform. We now explore the utility of albumin ISH as a marker of hepatocellular differentiation in HCCs, and compare its sensitivity with Hep Par 1 and Arginase-1. We evaluated 93 HCCs and its mimics including neuroendocrine tumors of the gastrointestinal tract (n=31), neuroendocrine tumors of the pancreas (n=163), melanoma (n=15), and gallbladder carcinoma (n=34). We performed ISH for albumin and immunohistochemistry for Hep Par 1 and Arginase-1. Five previously uncharacterized hepatic neoplasms from our files were also evaluated. Immunohistochemistry for Arginase-1 was performed on 59 intrahepatic cholangiocarcinomas. In addition, 43 HCCs evaluated on the manual platform were also examined on the automated instrument. Fifty-five percent of HCCs were moderately differentiated and 39% poorly differentiated. The sensitivity of ISH for albumin was 99%, with 92 of 93 HCCs staining positive for albumin. In contrast to ISH, the sensitivity of immunohistochemistry for Hep Par 1 and Arginase-1 was 84% and 83%, respectively. The sensitivity of albumin for poorly differentiated HCCs was 99%, whereas that for Arginase-1 and Hep Par 1 was 71% and 64%, respectively. Ninety-seven percent of the HCCs showed albumin positivity in >50% of tumor cells using the ISH platform, as compared with 76% and 70% for Hep Par 1 and Arginase-1 immunohistochemistry, respectively. Three of the 5 previously uncharacterized neoplasms were positive for albumin ISH. Automated albumin ISH platform performed equivalently to the manual format, with albumin reactivity in >50% of tumor cells in all 43 cases that were tested on both platforms. All non-HCCs were negative for albumin. All 59 intrahepatic cholangiocarcinomas were negative for Arginase-1. In conclusion, branched chain ISH performed on manual and automated mode is a robust assay for detecting albumin with sensitivity for poorly differentiated HCCs superior to Arginase-1 and Hep Par 1. When interpreted in conjunction with Arginase-1, albumin ISH offers a high level of sensitivity and specificity.
    American Journal of Surgical Pathology 10/2014; 39(1). DOI:10.1097/PAS.0000000000000343 · 4.59 Impact Factor