Diagnostic utility of the HepPar1 antibody to differentiate hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration samples

Siddiqui, Momin T.; Hossein, M.; Gokaslan, Sefik T.; Ashfaq, Raheela

doi:10.1002/cncr.10311.abs

Cited by 25 publications

(41 citation statements)

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“…The expression of CPS1 is generally diminished in HCC. 8 In our study, it is clear that CPS1 expression is suppressed in HCC cells and tumor tissues. Because CPS1 expression is liver specific, one potential reason for the down-regulation is probably because of loss of hepatocellular differentiation in HCC, thus the reduction of liver-specific transcription factors.…”

Section: Discussionmentioning

confidence: 58%

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DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma

Liu

Dong

Robertson

et al. 2011

The American Journal of Pathology

104

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Carbamoyl phosphate synthetase 1 (CPS1) is a liverspecific, intramitochondrial, rate-limiting enzyme in the urea cycle. A previous study showed that CPS1 is the antigen for hepatocyte paraffin 1 antibody, a commonly used antibody in surgical pathology practice; and CPS1 expression appears to be down-regulated in liver cancer tissue and cell lines. The aim of this study is to understand how the CPS1 gene is regulated in liver carcinogenesis. In this report, we show that human hepatocellular carcinoma (HCC) cells do not express CPS1, whereas cultured human primary hepatocytes express abundant levels. In addition, CPS1 was silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues. The expression of CPS1 in HCC cells was restored with a demethylation agent, 5-azacytidine. We show that two CpG dinucleotides, located near the transcription start site, and a CpG-rich region in the first intron were hypermethylated in HCC cells. The hypermethylation of the two CpG dinucleotides was also detected in HCC tumor tissues compared with noncancerous tissues. Further molecular analysis with mutagenesis indicated that the two CpG dinucleotides play a role in promoter activity of the CPS1 gene. In conclusion, our study demonstrates that DNA methylation is a key mechanism of silencing CPS1 expression in human HCC cells, and CPS1 gene hypermethylation of the two CpG dinucleotides is a potential biomarker for HCC.

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Section: Discussionmentioning

confidence: 58%

“…7 During that study, we noticed that the CPS1 protein was not detectable in human hepatocellular carcinoma (HCC) cell lines while the CPS1 gene is intact. Other researchers 8 have reported that 75% of human HCC tissues express low levels of CPS1. However, the underlying mechanisms of CPS1 dysregulation in HCC are completely unknown.…”

mentioning

confidence: 88%

DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma

Liu

Dong

Robertson

et al. 2011

The American Journal of Pathology

104

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“…20 In addition to hematoxylin and eosin staining, the cell block paraffin sections also were used for reticulin stain. 21 In difficult cases, immunohistochemical stains, including CD34, 22 polyclonal carcinoembryonic antigen (CEA), 23 Hepar-1, 24 and MIB-1, also were performed using the standard avidin-biotin-peroxidase method.…”

Section: Methodsmentioning

confidence: 99%

Cytologic features and histologic correlations of microacinar and microtrabecular types of well-differentiated hepatocellular carcinoma in fine-needle aspiration biopsy

Yang

Tao

2003

Cancer

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“…The current literature shows that difficulties in histological typing of liver tumors, particularly in the differential diagnosis between HCC and CC and metastases can be minimized by using immunohistochemistry [4,6] . Among the numerous diagnostic immunohistochemical markers studied, alphafetoprotein (AFP) [7] , CK7 [8] , CK20 [9] , CK19 [10] , hepatocyte paraffin 1 (Hep Par 1) [11,12] and glypican 3 (GPC3) [3,5,13] have been found to be valuable in the diagnosis of HCC. The sensitivity and specificity of the monoclonal antibody Hep Par 1 for HCC are considered ver y high; as a consequence, the usefulness of this marker in the differential diagnosis of hepatic tumors is widely accepted [14,15] , although it stains normal hepatocytes as well.…”

Section: Introductionmentioning

confidence: 99%

Intratumoral sampling variability in hepatocellular carcinoma: A case report

Senes

Fanni²,

Cois³

et al. 2007

WJG

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The differential diagnosis between hepatocellular carcinoma (HCC) and regenerative liver nodules and other primary liver tumors may be very difficult, particularly when performed on liver biopsies. Difficulties in histological typing may be often minimized by immunohistochemistry. Among the numerous markers proposed, CK18, Hep Par1 and glypican 3 (GPC3) are considered the most useful in HCC diagnosis. Here we report a case of HCC in a 72-year-old male with HBVrelated chronic liver disease, characterized by a marked morphological and immunohistochemical intratumoral variability. In this case, tumor grading ranged from areas extremely well differentiated, similar to regenerative nodule, to undifferentiated regions, with large atypical multinucleated cells. While almost all sub nodules were immunostained by Hep Par 1, immunoreactivity for glypican 3 and for Ck18 was patchy, with negative tumor region adjacent to the highly immunoreactive areas. Our case stresses the relevance of sampling variability in the diagnosis of HCC, and indicates that caution should be taken in grading an HCC and in the interpretation of immunohistochemical stains when only small core biopsies from liver nodules are available.

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Diagnostic utility of the HepPar1 antibody to differentiate hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration samples

Cited by 25 publications

References 0 publications

DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma

DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma

Cytologic features and histologic correlations of microacinar and microtrabecular types of well-differentiated hepatocellular carcinoma in fine-needle aspiration biopsy

Intratumoral sampling variability in hepatocellular carcinoma: A case report

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