title: Anterior gradient-2 is overexpressed by fibrolamellar carcinomas.
abstract: Anterior gradient-2 expression is critical in normal embryonic development. Aberrant expression of anterior gradient-2 in adult tissues has been linked to breast, prostate, esophageal, and pancreatic carcinoma. To define the role of anterior gradient-2 in primary hepatocellular neoplasms, we used tissue microarrays and examined protein expression in typical hepatocellular carcinomas (n = 44), fibrolamellar carcinomas (n = 12), and hepatic adenomas (n = 9). In nonneoplastic liver tissues, anterior gradient-2 was expressed in the septal-sized bile ducts and weakly in zone 3 hepatocytes in 11 (18%) of 61 cases. In tumors, anterior gradient-2 was overexpressed by only 1 (2%) of 44 hepatocellular carcinomas. In contrast, 6 (75%) of 8 fibrolamellar and 3 (75%) of 4 metastatic fibrolamellar carcinomas were positive. All 9 hepatic adenomas were negative. Further analysis of mRNA in fibrolamellar carcinomas identified 2 novel splice variants, but expression levels were very low. Sequencing of the anterior gradient-2 gene in fibrolamellar carcinomas identified several polymorphisms (refSNP Ids: rs6842, rs8071, rs1051905) but no mutations. In conclusion, anterior gradient-2 is overexpressed in the majority of fibrolamellar carcinomas but is only rarely overexpressed in hepatocellular carcinomas.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Perumal
authors.initials: P
authors.lastname: Vivekanandan
authors.forename: Shien T L
authors.initials: ST
authors.lastname: Micchelli
authors.forename: Michael
authors.initials: M
authors.lastname: Torbenson
mesh_terms: D018248:Adenoma, Liver Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009088:Mucoproteins; D015513:Oncogene Proteins; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: C502296:AGR2 protein, human; D014408:Biomarkers, Tumor; D009088:Mucoproteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; D011506:Proteins