Utility of Bile Salt Export Pump Transporter Immunohistochemistry Compared to Other Hepatocellular Markers for the Diagnosis of Hepatocellular Carcinoma
Thuy Nguyen, Daniel Phillips, Sanjay Kakar. UCSF, San Francisco, CA
Background: Bile salt export pump transporter (BSEP) is encoded by the ABCB11 gene and is expressed on the apical side of the bile canalicular membrane in hepatocytes. The role of BSEP for the diagnosis of hepatocellular carcinoma (HCC) has been suggested but not explored in detail.
Design: Immunohistochemistry for BSEP was performed on 71 HCC. The cases were stratified into well differentiated (WD, n=13), moderately differentiated (MD, n=35) and poorly differentiated (PD, n=23) HCC based on WHO criteria. More than one differentiation pattern was seen in 12 cases; these were scored separately yielding 83 observations. Canalicular staining pattern with BSEP was considered positive. The staining intensity was recorded on a scale of 0-3; 2+ or 3+ staining in >5% of tumor cells was considered positive. The results were compared with other hepatocellular markers that had been previously done in the same cases: Hep Par 1 (Hep), polyclonal CEA (pCEA), glypican-3 (GPC) and arginase-1 (Arg).
Results: When staining of >5% of tumor was considered positive, BSEP had a sensitivity of 76% (92% in WD-HCC, 95% in MD-HCC, and 45% in PD-HCC). When staining of >50% of tumor was considered positive, the overall sensitivity of BSEP decreased to 47% (69% in WD-HCC, 72% in MD-HC, and 6% in PD-HCC). Membrane staining with BSEP was seen in 8 (9.6%) HCCs, which obscured the canalicular staining pattern. BSEP was similar to Arg, Hep and pCEA in WD and MD HCC. For PD HCC, the sensitivity was lower compared to GPC and Arg. The addition of BSEP to other hepatocellular markers did not lead to increase in sensitivity for any differentiation.