HepPar-1 is a mitochondrial antigen present in normal hepatocytes, and is a relatively specific marker for hepatic origin.  It also stains approximately 80-100% of hepatocellular carcinomas.  It is most commonly used to help identify tumors of primary hepatic origin, and exclude cholangiocarcinoma in the differential diagnosis. 

The staining pattern is granular and cytoplasmic in location.  The staining pattern can be heterogeneous ranging from focal (<5%) in poorly differentiated HCC to strong diffuse staining in well-differentiated HCC.  As with most issues in pathology and IHC, less differentiated lesions more often need IHC, which tend to perform less-optimally than described in the literature (case selection bias).  Also beware of focal staining of benign entrapped hepatocytes.

HepPar-1 is not a pertfectly specific marker for HCC.  One study (Wee) notes specificity as 73% with non-hepatic tumors including adenocarcinomas from lung, gallbladder, pancreas, stomach, small intestine, adenoma of colon, adrenal gland carcinoma, paraganglioma, and melanoma showing expression.  Other studies show the specificity near 90% for HCC.

 

Up to 25% (probably <10% overall) of lung carcinomas (mostly adenocarcinomas) have been noted to have HepPar1 expression (cytoplasmic and granular).  The expression pattern may be focal/patchy, but these tumors also typically express TTF-1.

 

Use of HepPar-1 as part of a panel (and clinical-radiologic correlation) is recommended for optimal interpretation. 

Wee, A. (2006). Diagnostic utility of immunohistochemistry in hepatocellular carcinoma, its variants and their mimics. Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 14(3), 266–272.

 

Allende, D., & Yerian, L. (2009). Immunohistochemical Markers in the Diagnosis of Hepatocellular Carcinoma. Pathology Case Reviews, 14(1), 40–46.

 

Yousem, S. A., Lale, S., & Dacic, S. (2013). HepPar-1 expression in primary lung adenocarcinoma. American Journal of Clinical Pathology, 140(2), 225–230. doi:10.1309/AJCP4MXTNQRVOE2T

 

Minervi el al., 1997.  

 

Chu et al., Am J Surg Pathol 26:978-88, 2002.

 

L. Lamps. “The Differential Diagnosis of Hepatic Tumors.”  UAMS, Lecture, 2005.