Hepatocellular Carcinoma, Renal Cell Carcinoma Metastatic to Liver, and Adrenal Carcinoma Metastatic to Liver: Immunostaining for Bile Salt Export Pump as a Marker of Hepatocellular Differentiation
AS Knisely. King's College Hospital, London, United Kingdom
Background: Bile salt export pump (BSEP) is an ATP-binding cassette transporter normally expressed only at the apical (canalicular) membrane of hepatocytes. If BSEP expression persists in hepatocellular neoplasms, to detect BSEP immunohistochemically might be useful in identifying hepatocellular differentiation.
Design: Formalin-fixed, paraffin-embedded archival samples of 25 tumours resected from liver and assessed on clinicopathologic grounds as hepatocellular carcinoma (HCC; 15), renal cell carcinoma metastatic to liver (RCC; 5), and adrenal cortical carcinoma metastatic to liver (ACC; 4) were immunostained for BSEP by standard techniques, using a polyclonal, affinity-purified antibody raised in rabbit. Degrees of HCC differentiation covered a spectrum from cells with minimal nuclear pleomorphism, resembling hepatocytes and rosetted around accumulations of material resembling bile (well-differentiated), to cells with extreme nuclear pleomorphism and scant and amphophilic or clear cytoplasm, lacking resemblance to hepatocytes and disposed without evident secondary structure (poorly differentiated). Using commercially available antibodies, parallel sections were immunostained for 5 additional canalicular antigens, including 2 transport proteins homologous to BSEP, multiple drug resistance associated protein 2 (MRP2; lacking in the Dubin-Johnson syndrome) and multidrug resistance protein 3 (MDR3; lacking in several cholestatic disorders); 2 ectoenzymes, neutral endopeptidase (CD10) and alanyl aminopeptidase (CD13); and carcinoembryonic antigen (using a polyclonal antibody; pCEA), as well as for the hepatocyte-associated cytoplasmic antigen carbamoyl phosphate synthetase (CPS; OCH1E5 / HepPar-1). Expression was scored as present or absent, with 3 descriptors (polarised membranous, diffuse membranous, and cytoplasmic).
Results: In HCC, polarised canalicular-antigen expression (BSEP, CD10, CD13, pCEA, MDR3, MRP2) was lost as differentiation worsened. CPS expression persisted in some moderately poorly differentiated HCC but was lost in worst-differentiated HCC. RCC expressed CD10, CD13, pCEA, MRP2, and MDR3, but not BSEP or CPS; ACC expressed only pCEA.
Conclusions: Unlike other canalicular antigens, BSEP expression in neoplasms appeared specific for hepatocellular differentation. It was, however, less robust than CPS expression. To immunostain for BSEP expression may have limited diagnostic value in relatively well-differentiated tumours.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 177, Tuesday Morning