Table 1.
Marker | Staining pattern | Expected staining | Advantages | Disadvantages |
LFABP | Cytoplasmic/nuclear | Normal: Diffuse | Can subclassify HCA | |
H-HCA: Negative | ||||
SAA | Cytoplasmic | Normal: Negative | Can subclassify HCA | |
IHCA: Strong | ||||
GS | Cytoplasmic | Normal: Perivenular | Can subclassify HCA | Not specific for β-HCA (other HCA sub-types can stain) |
FNH: Map-like | HCA and HCC have similar staining patterns | |||
β-HCA/HCC: Diffuse | Metastatic adenocarcinoma in liver usually positive | |||
HSP70 | Cytoplasmic/nuclear | Normal, HCA, H-DN: Negative | Suggestive of malignancy | Staining may be focal |
HCC: Positive | Metastatic adenocarcinoma frequently positive | |||
GPC-3 | Cytoplasmic/membranous | Normal: Negative | More sensitive in poorly differentiated tumors | Low sensitivity in well-differentiated tumors |
HCC: Positive | Marks scirrhous HCC | May not react with fibrolamellar HCC | ||
Only single marker which supports both hepatocellular differentiation and malignancy | ||||
CD34 | Cytoplasmic/membranous | Normal: Portal vessels, rare sinusoids | Can help demarcate extent of lesion | No specific cutoff for increased staining |
HCC: Diffuse capillarization | ||||
AFP | Cytoplasmic | Normal: Negative | High specificity for HCC | Low sensitivity |
HCC: Positive | ||||
p-CEA | Canalicular | Normal: Canalicular | High sensitivity and specificity for | May be difficult to interpret, since only |
HCC: Canalicular | hepatocytes when definite canalicular | canalicular pattern is specific for hepatocytes | ||
Metastatic ca: Any pattern other than canalicular | pattern present | |||
CD10 | Canalicular | Normal: Canalicular | High sensitivity and specificity for | May be difficult to interpret, since |
HCC: Canalicular | hepatocytes when definite canalicular | only canalicular pattern is specific for hepatocytes | ||
Metastatic ca: Any pattern other than canalicular | pattern present | |||
HepPar-1 | Cytoplasmic | Liver only | Marks cells of liver origin, both normal and neoplastic | Mediocre specificity, including any hepatoid lesion |
Less sensitive in poorly differentiated tumors | ||||
ARG-1 | Cytoplasmic/nuclear | Liver only | More sensitive and specific than HepPar-1 | Less sensitive in poorly differentiated tumors |
BSEP | Usually, but not exclusively canalicular | Normal, HCC: Canalicular (usually) with | High sensitivity and specificity for hepatocytes | New marker, pitfalls and disadvantages |
occasional dot-like or incomplete membranous pattern | Easier to interpret than other p-CEA and CD10 | currently unknown |
HCC: Hepatocellular carcinoma; HCA: Hepatocellular adenoma; H-DN: High-grade dysplastic nodules; p-CEA: Polyclonal carcinoembryonic antigen; H-HCA: HNF1α-inactivated HCA; LFABP: Liver fatty acid binding protein; GS: Glutamine synthetase; FNH: Focal nodular hyperplasia; SAA: Serum amyloid A; IHCA: Inflammatory HCA; GPC-3: Glypican-3; HSP70: Heat shock protein 70; HepPar-1: Hepatocyte paraffin 1; AFP: Alpha-fetoprotein; BSEP: Bile salt export pump; ARG-1: Arginase-1.