Bile Salt Export Pump (BSEP) is an ATP-binding cassette transporter protein (encoded by ABCB11) that functions as the major canalicular bile salt transporter in hepatocytes. In diagnostic pathology, BSEP IHC is used primarily as a canalicular marker for hepatocellular carcinoma and in the diagnosis of bile salt export pump deficiency in progressive familial intrahepatic cholestasis type 2 (PFIC2).
Hepatocellular carcinoma
BSEP shows a canalicular (“chicken-wire”) staining pattern in tumour cells, reflecting its normal physiological role as a bile salt transporter. This pattern confirms hepatocellular differentiation and helps distinguish HCC from metastatic adenocarcinoma or cholangiocarcinoma, neither of which forms canaliculi and therefore won’t show this staining pattern.
BSEP functions conceptually alongside other canalicular markers such as polyclonal CEA and CD10, and is generally considered more sensitive and specific than pCEA in some series.
Loss or reduction of BSEP staining has also been reported in poorly differentiated HCC and in some cholestatic hepatocellular lesions, so absent staining isn’t specific on its own — pattern interpretation in context matters.
Progressive Familial Intrahepatic Cholestasis Type 2
PFIC2 results from biallelic ABCB11 mutations. Liver biopsy IHC typically shows absent or markedly reduced canalicular BSEP staining, supporting the diagnosis alongside clinical/biochemical features (low-GGT cholestasis, elevated bile acids) and molecular confirmation.
A useful nuance: some ABCB11 missense mutations produce a mistrafficked but partially functional protein, which can show weak/patchy canalicular staining or an intracellular rather than purely canalicular pattern — so BSEP IHC is supportive but not strictly binary, and genetic testing remains the gold standard.
PFIC2 patients with BSEP deficiency also carry an increased risk of hepatocellular carcinoma and cholangiocarcinoma at a young age, which is relevant when assessing paediatric explant or resection specimens.