Bile salt export pump: a sensitive and specific immunohistochemical marker of hepatocellular carcinoma

Bile salt export pump (BSEP) is a transporter expressed exclusively at hepatic canaliculi and drives bile-salt efflux. Minimal data exist about BSEP expression in tumours. We hypothesized that BSEP immunohistochemistry would be specific for hepatocellular carcinoma (HCC).

Tissue microarrays, including 48 HCC, 41 cholangiocarcinomas and 24 metastatic tumours in liver, were immunostained for BSEP. Expression was compared with common markers of hepatocytic differentiation including CD10, hepatocyte paraffin-1 antigen (HepPar-1), carcinoembryonic antigen, arginase-1 (ARG) and glypican-3 (GPC-3). BSEP expression was assessed in normal tissues. Special attention was given to adrenal gland (normal and neoplasia). BSEP was easy to interpret and showed no background staining. Canalicular expression was seen in all normal livers, but not in other normal tissue. BSEP was 90% sensitive and 100% specific for HCC (canalicular in 33 of 43 positive cases). The sensitivity of ARG was slightly higher, but specificity was slightly lower (94% for both). HepPar-1 was 90% sensitive and 97% specific. CD10, polyclonal carcinoembryonic antigen (pCEA) and GPC-3 all had lower sensitivity (74, 81 and 54%, respectively).

In malignant tumours in the liver, BSEP marking was 100% specific and 90% sensitive for HCC. The specificity of BSEP for HCC obviates the need to identify a 'canalicular' pattern, which can limit the utility of other canalicular markers.