Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study

Villari, Daniela; Caruso, Rosario Alberto; Grosso, Maddalena; Vitarelli, Enrica; Righi, Maria; Barresi, G

doi:10.1080/0031302021000009333

Cited by 37 publications

(27 citation statements)

References 5 publications

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“…11 Rare examples of cholangiocarcinomas, yolk sac tumor, and adenocarcinomas of the ovary, adrenal cortex, lung, endocervix, colon, and pancreas have shown focal Hep Par 1 staining. 9,12,13 Hep Par 1 reactivity is also seen in benign small intestinal mucosa and intestinal metaplasia of the esophagus and stomach. the identity of the antigen and its role in liver biology and carcinogenesis are still unknown, constituting one of the great enigmas of diagnostic pathology.…”

mentioning

confidence: 96%

The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1

Butler

Dong

Cardona

et al. 2008

Laboratory Investigation

116

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Hepatocyte paraffin 1 (Hep Par 1), a murine monoclonal antibody, is widely used in surgical pathology practice to determine the hepatocellular origin of neoplasms. However, identity of the antigen for Hep Par 1 is unknown. The aim of this study was to characterize the Hep Par 1 antigen. To identify the antigen, immunoprecipitation was used to isolate the protein from human liver tissue, and a distinct protein band was detected at approximately 165 kDa. The protein band was also present in small intestinal tissue, but was not present in several other non-liver tissues nor in three human hepatocellular carcinoma cell lines, Huh-7, HepG2, and LH86. The protein was purified and analyzed by mass spectrometry. It was identified as carbamoyl phosphate synthetase 1 (CPS1). CPS1 is a rate-limiting enzyme in urea cycle and is located in mitochondria. We demonstrated that hepatoid tumors (gastric and yolk sac) were immunoreactive with both Hep Par 1 antibody and anti-CPS1 antibody, further confirming the results of mass spectrometric analysis. We found that the three human hepatocellular carcinoma cell lines do not express either CPS1 RNA or protein. We confirmed that the gene was present in these cell lines, suggesting that suppression of CPS1 expression occurs at the transcriptional level. This finding may have relevance to liver carcinogenesis, since poorly differentiated hepatocellular carcinomas exhibit poor to absent immunoreactivity to Hep Par 1. In conclusion, we have identified the antigen for Hep Par 1 antibody as a urea cycle enzyme CPS1. Our results should encourage further investigation of potential role that CPS1 expression plays in liver pathobiology and carcinogenesis. The histological distinction between hepatocellular carcinomas (HCC) and metastatic adenocarcinoma to the liver can sometimes be a challenging dilemma for surgical pathologists, particularly given the histological variants of HCC that can occur. In addition, tumors in other sites can display hepatoid morphologic features, adding to the diagnostic challenge when considering their metastasis to the liver. In the end, a wide panel of immunohistochemical markers is often used for the differential diagnosis of HCC, cholangiocarcinoma and metastatic adenocarcinoma. These markers include alpha-fetoprotein (AFP), polyclonal carcinoembryonic antigen (pCEA), and alpha-1-antitrypsin.

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mentioning

confidence: 96%

The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1

Butler

Dong

Cardona

et al. 2008

Laboratory Investigation

116

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“…However, most large studies have demonstrated expression, even at high levels, in a small but significant (1%-10%) subset of adenocarcinomas primary to the lung, pancreas, stomach, ovaries, and adrenal cortex, 110,112 making it important to use the Hep-Par 1 antibody as part of a panel of antibodies in determining the most likely primary site; these Hep-Par 1 þ tumors are frequently, albeit not exclusively, tumors with hepatoid morphology. 115,116 Because expression of CPS1 is observed in nonneoplastic liver and benign hepatocellular lesions, the use of Hep-Par 1 antibody cannot be used to distinguish benign from malignant liver lesions.…”

Section: 106mentioning

confidence: 99%

Practical Applications in Immunohistochemistry: Carcinomas of Unknown Primary Site

Kandalaft

Gown

2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Identification of the site of origin of carcinoma of unknown primary using immunohistochemistry is a frequent requirement of anatomic pathologists. Diagnostic accuracy is crucial, particularly in the current era of targeted therapies and smaller sample sizes.Objectives.-To provide practical guidance and suggestions for classifying carcinoma of unknown primary using both proven and new antibodies, as well as targeting panels based on integration of morphologic and clinical features.Data Sources.-Literature review, the authors' practice experience, and authors' research.Conclusions.-With well-performed and interpreted immunohistochemistry panels, anatomic pathologists can successfully identify the site of origin of carcinoma of unknown primary. It is crucial to understand not only the diagnostic uses of the many available antibodies but also the potential limits and pitfalls.

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“…The expression profiles of the various mucins are also highly variable and of limited utility in the separation of CRC from GA [136,137]. More useful markers include nuclear β-catenin, which has not been identified in GA in limited studies, and Hep Par-1, which has been identified in 50% of cases [138]. Studies examining CK17 expression in GA have demonstrated positivity in 0% to 28% [6][7][8].…”

Section: Gastric Adenocarcinomamentioning

confidence: 98%

Immunohistochemistry of colorectal carcinoma: current practice and evolving applications

2013

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Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study

Cited by 37 publications

References 5 publications

The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1

The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1

Practical Applications in Immunohistochemistry: Carcinomas of Unknown Primary Site

Immunohistochemistry of colorectal carcinoma: current practice and evolving applications

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