title: Comparison of 5 Immunohistochemical Markers of Hepatocellular Differentiation for the Diagnosis of Hepatocellular Carcinoma.
abstract: BACKGROUND
  Several immunohistochemical markers are available to establish the diagnosis of hepatocellular carcinoma. Judicious selection is essential to achieve a reliable diagnosis in limited tissue provided by liver biopsy.
  
  
  OBJECTIVE
  To compare the efficacy of 5 hepatocellular markers for the diagnosis of hepatocellular carcinoma across various levels of differentiations.
  
  
  METHODS
  Immunohistochemistry for hepatocyte paraffin antigen 1 (Hep Par 1), polyclonal carcinoembryonic antigen (CEA), glypican-3, arginase-1, and bile salt export pump transporter was performed in 79 hepatocellular carcinomas, yielding 93 observations (13 well-differentiated [14%], 41 moderately differentiated [44%], and 39 poorly differentiated [42%] tumors).
  
  
  RESULTS
  Arginase-1 and Hep Par 1 had the highest sensitivity for well-differentiated hepatocellular carcinoma, whereas arginase-1 and glypican-3 had the highest sensitivity for poorly differentiated hepatocellular carcinoma. When staining of more than 50% of the tumor was considered a positive result, arginase-1 remained the most sensitive marker for all differentiations, whereas sensitivity for Hep Par 1 in poorly differentiated hepatocellular carcinoma dropped to 30% and that of glypican-3 in well-differentiated hepatocellular carcinoma was 15%. The addition of Hep Par 1 and/or polyclonal CEA to arginase-1 did not lead to an increase in sensitivity for any differentiation. The combined use of arginase-1 and glypican-3 yielded 100% sensitivity for poorly differentiated hepatocellular carcinoma.
  
  
  CONCLUSIONS
  Arginase-1 was the most sensitive marker in all differentiations of hepatocellular carcinoma. Glypican-3 had high sensitivity for poorly differentiated cases and its combined use with arginase-1 enabled identification of nearly all cases of poorly differentiated hepatocellular carcinoma. Although bile salt export pump transporter has good overall sensitivity, it has a limited role in establishing hepatocellular differentiation when added to a panel of arginase-1 with either glypican-3 or Hep Par 1.
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.forename: Daniel
authors.initials: D
authors.lastname: Phillips
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Jain
authors.forename: Michael
authors.initials: M
authors.lastname: Torbenson
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: From the Department of Anatomic Pathology, University of California, San Francisco, (Drs Nguyen, Phillips, and Kakar); the Department of Pathology, Yale University School of Medicine, New Haven, Connecticut (Dr Jain); the Department of Pathology, Johns Hopkins, Baltimore, Maryland (Dr Torbenson); the Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota (Dr Wu); the Department of Pathology, University of Washington, Seattle, (Dr Yeh); and the Department of Anatomic Pathology, Veteran Affairs Medical Center, San Francisco (Dr Kakar).
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor