title: Expression of liver fatty acid binding protein in hepatocellular carcinoma.
abstract: Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down-regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Ferrell
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143. Electronic address: ryan.gill@ucsf.edu.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Gill
mesh_terms: D018248:Adenoma, Liver Cell / Q000737:chemistry / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000209:etiology / Q000473:pathology; D002454:Cell Differentiation; D003937:Diagnosis, Differential; D015536:Down-Regulation; D050556:Fatty Acid-Binding Proteins / Q000032:analysis*; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha
keywords: HNF1A; Hepatocellular adenoma; Hepatocellular carcinoma; Liver fatty acid binding protein; Well differentiated hepatocellular neoplasm