Current concepts in the immunohistochemical evaluation of liver tumors

Table 1 Immunohistochemical stains in liver tumors

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.