Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma

Krings, Gregor; Ramachandran, Rageshree; Jain, Dhanpat; Wu, Tsung Teh; Yeh, Matthew M.; Torbenson, Michael; Kakar, Sanjay

doi:10.1038/modpathol.2012.243

Cited by 76 publications

(54 citation statements)

References 46 publications

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“…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. 21 In addition, Arg-1 was expressed in all well and moderately differentiated cases, making it an excellent hepatocellular marker for both ends of the differentiation spectrum. In most cases that were Arg-1 þ , the staining was diffuse, indicating that this marker will yield similarly high sensitivity in biopsies.…”

Section: Commentmentioning

confidence: 99%

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

Nguyen

Phillips

Jain

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Several immunohistochemical markers are available to establish the diagnosis of hepatocellular carcinoma. Judicious selection is essential to achieve a reliable diagnosis in limited tissue provided by liver biopsy.Objective.-To compare the efficacy of 5 hepatocellular markers for the diagnosis of hepatocellular carcinoma across various levels of differentiations.Design. Results.-Arginase-1 and Hep Par 1 had the highest sensitivity for well-differentiated hepatocellular carcinoma, whereas arginase-1 and glypican-3 had the highest sensitivity for poorly differentiated hepatocellular carcinoma. When staining of more than 50% of the tumor was considered a positive result, arginase-1 remained the most sensitive marker for all differentiations, whereas sensitivity for Hep Par 1 in poorly differentiated hepatocellular carcinoma dropped to 30% and that of glypican-3 in well-differentiated hepatocellular carcinoma was 15%. The addition of Hep Par 1 and/or polyclonal CEA to arginase-1 did not lead to an increase in sensitivity for any differentiation. The combined use of arginase-1 and glypican-3 yielded 100% sensitivity for poorly differentiated hepatocellular carcinoma.Conclusion.-Arginase-1 was the most sensitive marker in all differentiations of hepatocellular carcinoma. Glypican-3 had high sensitivity for poorly differentiated cases and its combined use with arginase-1 enabled identification of nearly all cases of poorly differentiated hepatocellular carcinoma. Although bile salt export pump transporter has good overall sensitivity, it has a limited role in establishing hepatocellular differentiation when added to a panel of arginase-1 with either glypican-3 or

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Section: Commentmentioning

confidence: 99%

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

Nguyen

Phillips

Jain

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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“…It is supposed to have a better prognosis than IHCCA. 35 Recently, Krings et al 22 studied 20 such tumors and found that 85% were positive for ARG1 and 79% were positive for GPC3, whereas only 26% were positive for HepPar1; 53% of the tumors were also positive for CK7, and 26% were positive for CK19.…”

Section: Arg1mentioning

confidence: 99%

“…[19][20][21] In addition, poorly differentiated HCC and some HCC variants may be difficult to discern based on morphology alone. 22 In these circumstances, IHC is not only helpful but necessary for accurate diagnosis. In our experience, the most effective IHC approach to address these problematic issues is to positively confirm hepatocellular differentiation in the tumor cells in conjunction with various tumor-specific markers (covered in other review articles in this 2-part special IHC series of articles) to exclude possible mimickers.…”

Section: Livermentioning

confidence: 99%

“…When all 3 markers are used simultaneously, they can identify almost all HCCs, including rare variants. 22 However, caution is still warranted when the combination of these markers is used to differentiate metastatic carcinomas from HCC, particularly hepatoid carcinoma. In difficult scenarios, a distinction between primary HCC and metastasis has to be made on clinical grounds based on a patient's history and an imaging survey of most suspicious sites.…”

Section: Arg1mentioning

confidence: 99%

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Application of Immunohistochemistry in Gastrointestinal and Liver Neoplasms: New Markers and Evolving Practice

Chen

Lin

2015

Archives of Pathology &Amp; Laboratory Medicine

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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.

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“…HCC mimickers include some cases of adrenocortical carcinoma, renal cell carcinoma (RCC), large cell neuroendocrine carcinoma, clear cell sarcoma, melanoma and angiomyolipoma [4,5] . In addition, the poorly differentiated HCC may be difficult to identify based on morphology alone [6] .…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Distinction of Hepatocellular Carcinoma Using Arginase-1, Hepatocyte Paraffin Antigen -1 and Glypican-3

Hegazy

2016

Journal of Tumor

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of MC and negative in all cases of CC. Arginase-1 was more sensitive (87.5%) than HepPar-1 (71.9%) or GPC-3 (65.6%) for HCC. GPC-3 was more specific (93.8%) than HepPar-1 (87.5%) and arginase-1 (90.6%). However, the combination of the three biomarkers for the diagnosis of HCC raised the specificity to 100%. CONCLUSION: Arginase-1 and HepPar-1 are effective biomarkers for HCC differentiation. Also, arginase-1 demonstrates a superior sensitivity in comparison with GPC-3 and HepPar-1 in the diagnosis of HCC, whereas GPC-3 demonstrates superior specificity. Hence, the use of combination of arginase-1 with HepPar-1 and GPC-3 could be useful in the precise diagnosis of HCC and distinguishing it from non-HCC. INTRODUCTIONHepatocellular Carcinoma (HCC) is the most common primary cancer of liver, representing the third most common cause of cancer deaths all over the world [1] . Egypt has a high prevalence of HCC; it is the second most cancer site among males after cancer bladder and seventh among females [2] . Such high incidence has been attributed to the high prevalence of hepatitis C virus (HCV) amongst Egyptians [3] .Based on histological characters, most HCCs can be easily identified on hematoxylin and eosin stained sections. However, some types of benign and malignant tumors may share the morphologic features. HCC mimickers include some cases of adrenocortical carcinoma, renal cell carcinoma (RCC), large cell neuroendocrine carcinoma, clear cell sarcoma, melanoma and angiomyolipoma [4,5] . In ABSTRACT AIM: The distinction of hepatocellular carcinoma (HCC) from the metastatic carcinoma (MC) and intrahepatic cholangiocarcinoma (CC) often presents a diagnostic challenge that carries a significant impact on its subsequent management. In this study we aimed to evaluate the immunohistochemical expressions of arginase-1, hepatocyte paraffin antigen-1 (HepPar-1), and glypican-3 (GPC-3) in a trial to distinguish HCC from non-HCC involving the liver. MATERIALS AND METHODS:The study included 64 cases (32 HCC, 28 MC and 4 CC) and 5 specimens of normal liver tissues. These cases were investigated retrospectively from the archive of the Pathology Department, Zagazig University Hospitals. The predictive capacity of arginase-1, HepPar-1 and GPC-3 staining was determined using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) calculations. RESULTS: Both arginase-1 and HepPar-1 expressions were present in all cases of non-neoplastic hepatocellular tissues, whereas GPC-3 expression was absent in all cases. Only two of 28 (7.1%) cases of MC and one of 4 (25%) cases of CC showed positive immunoreactivity for arginase-1. HepPar-1 immunoreactivity was detected in 3 of 28 (10.7%) cases of MC and in one of 4 (25%) cases of CC. GPC-3 immunoreactivity was detected in 2 of 28 (7.1%) cases

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Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma

Cited by 76 publications

References 46 publications

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

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

Application of Immunohistochemistry in Gastrointestinal and Liver Neoplasms: New Markers and Evolving Practice

Immunohistochemical Distinction of Hepatocellular Carcinoma Using Arginase-1, Hepatocyte Paraffin Antigen -1 and Glypican-3

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