Table 1.

Stains for HCC

Stain/IHC	Primary Usefulness in HCC	Other Useful Findings	Comments
Reticulin	Highlights loss of normal cord architecture; referred to as “loss of reticulin”		Best used in comparison with nontumorous liver; easily misinterpreted and does not necessarily distinguish adenoma and HCC
K8 and K18	Keratins of hepatocytes; likely not positive in most adenocarcinomas
K7	May label cells in up to 50% of cases of HCC	Very strong and diffuse labeling is highly suggestive of biphenotypic differentiation
K20	Has been found in scattered cells in up to 20% of cases of HCC		Not useful in the K7/K20 algorithm for evaluating carcinomas
CD34	Labels the endothelial cells of the sinusoids of HCC but not nontumorous liver	Is a marker of “capillarization,” loss of endothelial cell fenestration	Caution: may be positive focally and/or diffusely in hepatocellular adenoma
pCEA	Labels canaliculi between benign and malignant hepatocytes; will not be as numerous as nontumorous liver	Cholangiocarcinoma is positive in cytoplasm	Nontumorous liver is strong positive control
CD10	Canalicular marker; specific but not as sensitive as pCEA	For clear cell carcinoma, CD10 can be useful to evaluate for cytoplasmic reactivity expected in renal cell carcinoma	Nontumorous liver is strong positive control
HEPAR1	Labels mitochondrial enzyme (granular) in mature hepatocytes; thus, may be negative in HCC		Very limited application in evaluation; may be positive in other cell types
GPC‐3	Useful when positive, not useful when negative; reported to be negative in hepatocellular adenoma		Caution: can be “patchy”; has been reported in chronic hepatitis C and in DNs
GS	Useful when positive, not useful when negative; may be positive in adenoma	Zone 3 hepatocytes are normally strongly positive for GS	Characteristic “map‐like” pattern in FNH
HSP70	Useful in combination with GPC‐3 and GSa		Caution: may be positive in DNs
Annexin‐2	Positive in hepatocytes and/or sinusoids		Caution: may also be positive in similar patterns in DNs and hepatocellular adenoma

Abbreviations: IHC, immunohistochemistry; K, keratin.

^aSee text.