Hep Par 1, Hepatocyte Paraffin 1
Hep Par 1 is a monoclonal antibody, clone OCH1E5.2.10. The antigen detected by Hep Par 1 does not appear to be an oncofetal antigen or tumour-associated antigen. There is preliminary evidence that it is associated with the membrane of hepatocyte mitochondria2 but absent from the mitochondria of other tissues.
The antibody is effective on formalin-fixed, paraffin embedded tissues. Antigen retrieval using high pH buffer and a detection kit which minimizes or eliminates non-specific biotin reactivity is recommended4. Staining is cytoplasmic and granular, without canalicular or zonal accentuation4.
Immunohistochemical expression
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Non-neoplastic hepatocytes show diffuse cytoplasmic staining with a distinct coarse granular pattern without canalicular accentuation. Bile ducts and non-parenchymal cells do not stain. Regenerative nodules show heterogeneous staining.
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Other normal human tissues are almost invariably negative. Normal small intestinal mucosa may show focal but intense staining2. The staining is restricted to absorptive cells, goblet and Paneth cells being negative16. Normal gastric and colonic mucosa are negative16.
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Intestinal metaplasia in both oesophagus and stomach is immunoreactive16
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columnar lined oesophagus without intestinal metaplasia
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0/216
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columnar lined oesophagus with intestinal metaplasia
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31/3116
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chronic gastritis with intestinal metaplasia
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13/1316
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.
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Staining of hepatocellular carcinoma is much more heterogeneous and corresponds to the degree of differentiation7,8,13,15. Sensitivity seems to be lower for the sclerosing variant of hepatocellular carcinoma. Limited experience suggests fibrolamellar variants are immunoreactive2.
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Combined hepatocellular and cholangiocarcinoma show staining restricted to the hepatocellular component.
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A minority of cases of cholangiocarcinoma are immunoreactive, with a granular pattern similar to that seen in hepatocellular carcinoma.
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hepatoid tumours of stomach, gallbladder and ovary are positive.
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hepatocellular carcinoma
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30/321,
37/38(1/1 sclerosing HCC was negative, 4 HCC only showed rare positive cells, 5/5 fibrolamellar HCC were positive)2, 289/2903, 17/215,
9/10(clear cell hepatocellular carcinoma)6, 12/127,
33/40(using cell blocks from FNAs, only positive in 56% of poorly differentiated HCCs)8, 6/910,
18/19(using tissue microarrays)11 , 39/4212,
88/96(positive in 50/50 grade 1 and 2 tumours, 37/44 grade 3 tumours and 1/2 grade 4 tumours)13,
50/76(2/2 grade 1, 28/38 grade 2, 17/28 grade 3, 2/7 grade 4 and 1/1 fibrolamellar.)15
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hepatoblastoma
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12/12(3 fetal, 2 embryonal and 7 mixed epithelial types)14, 1/15
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metastatic adenocarcinoma, NOS
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0/131, 1/185, 0/75 15
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biliary tract carcinoma
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4/321,
2/35(two cases showed minor focal positivity)2, 3/65,
0/3(using cell blocks from FNAs)8, 1/1413
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mixed hepatocellular carcinoma / cholangiocarcinoma
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0/35
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pancreatic carcinoma
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3/12(rare positive cells were seen in 2/2 mucinous cystadenocarcinomas and in one adenocarcinoma)2,
0/8(using cell blocks from FNAs)8, 1/1313
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breast carcinoma
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0/92,
0/6(using cell blocks from FNAs)8, 0/913
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oesophageal adenocarcinoma
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1/9(focal positivity in one case)16
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gastric carcinoma
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3/10(three cases showed focal but strong positivity)2, 10/1012, 4/1313,
1/8(the one positive case was a gastric adenocarcinoma, without hepatoid differentiation.)15,
4/13(3 of 12 intestinal carcinomas and 1 diffuse carcinoma)16
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small intestinal carcinoma
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0/62
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colon carcinoma
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0/8(an overlying villous adenoma was strongly positive)2,
1/10(using cell blocks from FNAs)8,
8/104(using tissue microarrays)11, 0/1013
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lung carcinoma
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0/52,
1/10(using cell blocks from FNAs)8,
3/55(using tissue microarrays)11, 0/612, 5/2113
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endometrial carcinoma
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0/32, 0/1013
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ovarian carcinoma
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0/72,
5/40(using tissue microarrays)11, 4/2413
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uterine cervix
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1/5(using tissue microarrays)11
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prostatic carcinoma
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0/42, 0/713
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renal carcinoma
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0/52, 0/106, 0/512, 0/1013, 0/7415
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hepatoid adenocarcinoma
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6/7(Staining was focal. 6 stomach and one gallbladder. These tumours were also positive for CEA and AFP)9,
2/6(hepatoid ovarian carcinomas)10
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hepatoid yolk sac tumour
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4/810
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adrenocortical carcinoma
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3/13(using tissue microarrays)11, 0/812, 0/1013, 0/2115
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small cell carcinoma of lung and skin
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0/1513
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salivary gland
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0/1913
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germ cell
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0/1413
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yolk sac tumour
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2/9(using tissue microarrays)11
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urinary bladder
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0/12, 1/1012, 0/1513
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vascular liver tumour
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0/52
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melanoma
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0/32
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mesothelioma
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0/32, 0/1613
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neuroendocrine carcinoma
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0/142, 0/135, 4/913
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carcinoid
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1/1013
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phaeochromocytoma
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0/22
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testicular tumours
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0/22
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skin, basal cell carcinoma
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0/1013
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skin, Merkel cell carcinoma
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0/913
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skin, squamous cell carcinoma
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0/1013
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epithelioid sarcoma
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0/1013
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thymoma
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0/813
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thyroid
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0/1413
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Diagnostic utility
References
1 Leong, A. S., Sormunen, R. T., Tsui, W. M., Liew, C. T. Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology 1998;33:318-324.
2 Wennerberg, A. E., Nalesnik, M. A., Coleman, W. B. Hepatocyte paraffin 1: a monoclonal antibody that reacts with hepatocytes and can be used for differential diagnosis of hepatic tumors. Am J Pathol 1993;143;1050-4.
3 Wu, P. C., Fang, J. W., Lau, V. K., Lai, C. L., Lo, C. K., Lau, J. Y. Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. Am J Pathol 1996;149:1167-75.
4 Lamps, L.W. and Folpe, A.L. The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review. Adv Anat Pathol 2003;10:39-43.
5 Minervini, M.I., Demetris, A.J., Lee, R.G., Carr, B.I., Madariaga, J. and Nalesnik, M.A. Utilization of hepatocyte-specific antibody in the immunocytochemical evaluation of liver tumors. Mod Pathol 1997;10:686-92.
6 Murakata, L.A., Ishak, K.G. and Nzeako, U.C. Clear cell carcinoma of the liver: a comparative immunohistochemical study with renal clear cell carcinoma. Mod Pathol 2000;13:874-81.
7 Kumagai I et al. Immunoreactivity to monoclonal antibody, Hep Par 1, in human hepatocellular carcinomas according to histopathological grade and histologic pattern. Hepatology Research 2001;20:312-319.
8 Zimmerman, R.L., Burke, M.A., Young, N.A., Solomides, C.C. and Bibbo, M. Diagnostic value of hepatocyte paraffin 1 antibody to discriminate hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration biopsies of the liver. Cancer 2001;93:288-91.
9 Maitra, A., Murakata, L.A. and Albores-Saavedra, J. Immunoreactivity for hepatocyte paraffin 1 antibody in hepatoid adenocarcinomas of the gastrointestinal tract. Am J Clin Pathol 2001;115:689-94.
10 Pitman M et al. Hepatocyte paraffin 1 antibody cannot distinguish primary ovarian malignancies with hepatoid differentiation from metastatic hepatocellular carcinoma. Mod Pathol 2002;15:206A. (abstract)
11 Fan Z et al. HepPar-1 stain for the differential diagnosis of hepatocellular carcinoma: 613 tumors tested using tissue microarrays and conventional sections. Mod Pathol 2002;15:1178A. (abstract)
12 Muir T et al. Immunoreacitivity for hepatocyte paraffin 1 antibody in hepatic and extrahepatic tumors. Mod Pathol 2002;15:290A. (abstract)
13 Chu, P.G., Ishizawa, S., Wu, E. and Weiss, L.M. Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein. Am J Surg Pathol 2002;26:978-88.
14 Fasano, M., Theise, N.D., Nalesnik, M., Goswami, S., Garcia de Davila, M.T., Finegold, M.J. and Greco, M.A. Immunohistochemical evaluation of hepatoblastomas with use of the hepatocyte-specific marker, hepatocyte paraffin 1, and the polyclonal anti-carcinoembryonic antigen. Mod Pathol 1998;11:934-8.
15 Wieczorek, T. J., J. L. Pinkus, et al. (2002). "Comparison of thyroid transcription factor-1 and hepatocyte antigen immunohistochemical analysis in the differential diagnosis of hepatocellular carcinoma, metastatic adenocarcinoma, renal cell carcinoma, and adrenal cortical carcinoma." Am J Clin Pathol 118(6): 911-21.
16 Chu, P. G., Z. Jiang, et al. (2003). "Hepatocyte antigen as a marker of intestinal metaplasia." Am J Surg Pathol 27(7): 952-9.
This page last revised 13.1.2004.
©SMUHT/PW Bishop