[1741] Bile Salt Export Pump (BSEP): A Sensitive and Specific Marker of Hepatocytic Differentiation in Liver Tumors

Stephen M Lagana, Helen Remotti, Roger K Moreira. Columbia University Medical Center, New York, NY

Background: Bile salt export pump (BSEP) is an ATP-dependent transporter of bile acids expressed exclusively in hepatocyte canaliculi. BSEP has been shown to be expressed in some hepatocellular carcinomas (HCC) as well as in benign hepatocytic tumors, but its immunohistochemical (IHC) expression has not been evaluated as a diagnostic tool for the evaluation of neoplasms in liver.
Design: Tissue microarrays including: 48 HCC, 18 hepatocellular adenomas (HCA), 41 cholangiocarcinomas (ChCa), 23 metastatatic lesions (METS) (15 adenocarcinomas [colon-12; upper GI-1; pancreas-1; and breast-1]; and 8 neuroendocrine tumors [pancreas-2; small bowel-4; unknown-2]) were stained for BSEP (mouse monoclonal IgG2a, clone F-6, 1:100, Santa Cruz) and compared to other IHC markers used in this context, including CD10, HepPar-1, and glypican-3. BSEP expression was also assessed in normal tissue including breast, thyroid, lung, small intestinal, pancreas, thymus, breast, squamous mucosa, tonsil, lymph node, fat, testicle, prostate, and kidney.
Results: BSEP staining by immunohistochemistry was easy to interpret with no background staining.
Distinct canalicular expression was seen in all normal livers and HCA but was absent in all other normal tissue samples.
Staining in HCC was canalicular in most cases (33 of 43 positive cases).
3 of 5 HepPar-1-negative cases were positive for BSEP (all poorly differentiated HCCs).

Frequency of positivity in malignant tumors

	HCC (n=48)	ChCA(n=41)	METS (n=23)
BSEP	43 (89.6%)	0	0
CD10 (Canalicular only)	25 (52%)	0	0
HepPar-1	43 (89.6%)	2 (4.8%)	2 (8.6%)*
Glypican-3	30 (62.5%)	1 (2.4%)	1 (4.3%)^

*Positivity seen in metastatic adenocarcinoma from duodenum and neuroendocrine carcinoma from unknown primary and ^metastatic neuroendocrine carcinoma from pancreas.




Conclusions: BSEP was 100% specific and 90% sensitive for identification of hepatocytic tumors.
High specificity obviates the need for a “canalicular” pattern, which greatly limits the utility of other canalicular markers.
CD10 was 100% specific when definite canalicular staining was identified; however, membranous/cytoplasmic staining was observed in 41% of ChCa and 35% of METS and is often difficult to interpret.
BSEP is valuable in the immunohistochemical evaluation of tumors in liver.
Category: Liver

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 248, Tuesday Morning