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Open Access The Applicability of a Human Immunohistochemical Panel to Mouse Models of Hepatocellular Neoplasia

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Various immunohistochemical panels are used as aids to distinguish between primary hepatocellular malignancies and metastatic tumors and between benign lesions and carcinomas. We compared the immunohistochemical spectrum of hepatocellular lesions in mice with that of human hepatocellular carcinoma (HCC). Specifically, we compared the staining parameters of 128 murine foci of cellular alteration (FCA) and tumors (adenoma and HCC) from archival tissue blocks of 3 transgenic mouse models (LFABP–cyclin D1, Alb1–TGFβ1, and LFABP–cyclin D1 × Alb1–TGFβ1) with those of archival human HCC (n = 5). Antibodies were chosen according to their published performance and characterization in human hepatocellular tumor diagnosis and included: arginase 1 (Arg1), β-catenin, glutamine synthetase (GS), glypican 3, hepatocyte paraffin 1 (HepPar1), and cytokeratin 19 (CK19). GS was the single best immunostain for identifying hepatocellular tumors in mice, with 100% positive staining. Data showed a trend toward loss of normal function (staining) with Arg1, with a higher percentage of positive staining in FCA than in adenomas and HCC. All FCA lacked murine β-catenin nuclear translocation, which was present in 2 of the 7 adenomas and 22 of the 96 HCC tested. HepPar1 staining was lower than anticipated, except in trabecular HCC (16 of 22 samples were positive). Glyp3 stained very lightly, and only scattered CK19-positive cells were noted (4 of 44 cases of mouse trabecular HCC). Thus, GS appears to be the most useful marker for identifying neoplasia in the transgenic mouse models we tested and should be included in immunohistochemistry assessing hepatocellular neoplasia development.

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Document Type: Research Article

Affiliations: 1: Department of Pathology, Microbiology, and Immunology, Section on Comparative Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [email protected] 2: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA 3: Department of Surgery, Division of Surgical Oncology, and Radiology, Division of Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA

Publication date: October 1, 2015

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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