Hep Par 1 (Hepatocyte Marker)

Sources/Clones
Dako (OCH 1E5).

Fixation/Preparation
The antibody is immunoreactive in fixed paraffin-embedded sections and immunoreactivity is slightly enhanced following HIER.

Background
Hep Par 1 (hepatocyte paraffin 1) is an IgGK antibody to both normal and neoplastic hepatocytes raised at the Pittsburgh Cancer Institute. Hep Par 1 detects an antigen that is localized to the hepatocyte cytoplasm and produces no staining of bile ducts or other non-parenchymal cells. The staining is granular, occasionally ring-like and is seen diffusely throughout the hepatocyte cytoplasm, without canalicular accentuation. There is no apparent zonal preference in normal liver. In the first paper documenting its specificity in human tissue sections, the antibody labeled 37 of 38 cases of hepatocellular carcinoma (HCC), although four tumors had only rare positivity. The negative case was an example of the sclerosing variant of hepatocellular carcinoma. Five examples of fibrolamellar variant were positive. Two of 31 cases of cholangiocarcinoma (CC) were positive for Hep Par 1 and the antibody also decorated three of ten cases of gastric carcinoma (Wennerberg et al, 1993). In our own recent study, Hep Par 1 labelled 31 of 32 HCCs as well as four of 27 cases of CC (Leong et al, 1998), but was not found in metastatic adenocarcinomas. One other study has employed Hep Par 1 and showed staining in 289 of 290 HCCs (Wu et al, 1996).

Applications
The highest diagnostic yield is obtained with Hep Par 1 when it is employed in a panel of antibodies in the context of the differential diagnosis (Appendix 1.8). Its main diagnostic application would be for the distinction of HCC from CC and metastatic adenocarcinoma in the liver. When employed with CK 19 and CK 20, it is able to provide useful diagnostic information to allow the separation of these three entities (Leong et al, 1998). CK 19 is largely limited to bile duct epitheliam and their corresponding neoplasms, including CC (Balaton et al, 1988; Terada et al, 1995), whereas CK 20 is a marker of gastrointestinal carcinomas, particularly those from the colon and, less consistently, the upper gastrointestinal tract and pancreas (Mietinen, 1995).

Comments
As the staining of Hep Par 1 is heterogeneous and may be focal within HCCs, caution should be exercised in interpretation as small biopsies such as needle cores may produce false-negative results. Despite its limitations, Hep Par 1 is still the best antibody yet for use in the differential diagnosis of liver carcinomas.

References
•Balaton AJ, Nehama-Sibony M, Gotheil C et al 1988. Distinction between hepatocellular carcinoma, cholangiocarcinoma, and metastatic carcinoma based on immunohistochemical staining for carcinoembryonic antigen and for cytokeratin 19 on paraffin sections. Journal of Pathology 156: 305-310.

•Leong AS-Y, Sormunen RT, Tsui WMS, Liew CT 1988. Immunostaining for liver cancers with special reference to Hap Par 1 antibody. Histopathology (in press 1998). reference to Hap Par 1 antibody. Histopathology (in press 1998).

•Miettinen M 1995. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. Modern Pathology 8: 384-388.

•Terada T, Hoso M, Nakanuma Y 1995. Distribution of cytokeratin 19-positive biliary cells in cirrhotic nodules, hepatic borderline nodules (atypical adenomatous hyperplasia), and small hepatocellular carcinomas. Modern Pathology 8: 371-379.

•Wennerberg AE, Nalesnik MA, Coleman WB 1993. Hepatocyte paraffin 1: a monoclonal antibody that reacts with hepatocytes and can be used for differential diagnosis of hepatic tumors. American Journal of Pathology 143: 1050-1054.

•Wu P-c, Fand JW-S, Lau VK-T et al 1996. Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. American Journal of Pathology 149: 1167-1175.

Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.