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

• 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.

• 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.

• Intestinal metaplasia in both oesophagus and stomach is immunoreactive¹⁶

	columnar lined oesophagus without intestinal metaplasia	0/216
	columnar lined oesophagus with intestinal metaplasia	31/3116
	chronic gastritis with intestinal metaplasia	13/1316

• .

• Staining of hepatocellular carcinoma is much more heterogeneous and corresponds to the degree of differentiation^7,8,13,15. Sensitivity seems to be lower for the sclerosing variant of hepatocellular carcinoma. Limited experience suggests fibrolamellar variants are immunoreactive².

• Combined hepatocellular and cholangiocarcinoma show staining restricted to the hepatocellular component.

• A minority of cases of cholangiocarcinoma are immunoreactive, with a granular pattern similar to that seen in hepatocellular carcinoma.

• hepatoid tumours of stomach, gallbladder and ovary are positive.

hepatocellular carcinoma 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 hepatoblastoma 12/12 (3 fetal, 2 embryonal and 7 mixed epithelial types)14, 1/15 metastatic adenocarcinoma, NOS 0/131, 1/185, 0/75 15 biliary tract carcinoma 4/321, 2/35 (two cases showed minor focal positivity)2, 3/65, 0/3 (using cell blocks from FNAs)8, 1/1413 mixed hepatocellular carcinoma / cholangiocarcinoma 0/35 pancreatic carcinoma 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 breast carcinoma 0/92, 0/6 (using cell blocks from FNAs)8, 0/913 oesophageal adenocarcinoma 1/9 (focal positivity in one case)16 gastric carcinoma 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 small intestinal carcinoma 0/62 colon carcinoma 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 lung carcinoma 0/52, 1/10 (using cell blocks from FNAs)8, 3/55 (using tissue microarrays)11, 0/612, 5/2113 endometrial carcinoma 0/32, 0/1013 ovarian carcinoma 0/72, 5/40 (using tissue microarrays)11, 4/2413 uterine cervix 1/5 (using tissue microarrays)11 prostatic carcinoma 0/42, 0/713 renal carcinoma 0/52, 0/106, 0/512, 0/1013, 0/7415 hepatoid adenocarcinoma 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 hepatoid yolk sac tumour 4/810 adrenocortical carcinoma 3/13 (using tissue microarrays)11, 0/812, 0/1013, 0/2115 small cell carcinoma of lung and skin 0/1513 salivary gland 0/1913 germ cell 0/1413 yolk sac tumour 2/9 (using tissue microarrays)11 urinary bladder 0/12, 1/1012, 0/1513 vascular liver tumour 0/52 melanoma 0/32 mesothelioma 0/32, 0/1613 neuroendocrine carcinoma 0/142, 0/135, 4/913 carcinoid 1/1013 phaeochromocytoma 0/22 testicular tumours 0/22 skin, basal cell carcinoma 0/1013 skin, Merkel cell carcinoma 0/913 skin, squamous cell carcinoma 0/1013 epithelioid sarcoma 0/1013 thymoma 0/813 thyroid 0/1413

Diagnostic utility

• Differentiation of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma

• Possibly for the identification of intestinal metaplasia in columnar lined oesophagus when goblet cells are sparse¹⁶.

References

¹Leong, 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.

²Wennerberg, 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.

³Wu, 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.

⁴Lamps, 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.

⁵Minervini, 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.

⁶Murakata, 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.

⁷Kumagai 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.

⁸Zimmerman, 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.

⁹Maitra, 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.

¹⁰Pitman 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)

¹¹Fan 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)

¹²Muir T et al. Immunoreacittvity for hepatocyte paraffin 1 antibody in hepatic and extrahepatic tumors. Mod Pathol 2002;15:290A. (abstract)

¹³Chu, 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.

¹⁴Fasano, 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.

¹⁵Wieczorek, 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.

¹⁶Chu, 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