title: Impaired autophagy response in human hepatocellular carcinoma.
abstract: BACKGROUND
  Autophagy is a cellular lysosomal degradation mechanism that has been implicated in chronic liver diseases and hepatocellular carcinoma (HCC). Association of autophagy defect with the development of human HCC has been shown in transgenic mouse model.
  
  
  OBJECTIVE
  We performed this study to verify whether a defect in autophagy would play a role in human hepatocellular carcinoma (HCC).
  
  
  METHODS
  Archival tissue sections of 20 patients with HCC with or without hepatitis C virus (HCV) infection were studied. All slides were immunostained using monoclonal antibodies to p62 and glypican-3 with appropriate positive and negative controls. The expression of p62 and glycican-3 in the HCC and the surrounding non-tumor was semiquantitated. The cytoplasmic staining was graded as negative, weak or strong.
  
  
  RESULTS
  Positive p62 staining was found in 20 out of 20 (100%) HCCs and negative staining was observed in 20 out of 20 non-tumor areas and cirrhotic nodules. Positive glypican-3 staining was found in 70% of HCCs and negative staining was seen in all non-tumor areas. An autophagy defect leading to increased expression of p62 and glypican-3 was also seen in the HCC cell line (Huh-7.5), but not in the primary human hepatocytes. Activation of cellular autophagy in Huh-7.5 cells efficiently cleared p62 and glypican-3 expression and inhibition of autophagy induced the expression of p62 and glypican-3.
  
  
  CONCLUSIONS
  This study shows that p62 is increased in HCC compared to the surrounding non-tumorous liver tissue suggesting that human HCCs are autophagy defective. We provide further evidence that glypican-3 expression in HCC may also be related to defective autophagy. Our study indicates that p62 immunostain may represent a novel marker for HCC.
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Partha K
authors.initials: PK
authors.lastname: Chandra
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Moroz
authors.affiliation: The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Xuchen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Swan N
authors.initials: SN
authors.lastname: Thung
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: sdash@tulane.edu.
authors.forename: Srikanta
authors.initials: S
authors.lastname: Dash
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D053673:Glypicans / Q000096:biosynthesis / Q000235:genetics*; D016174:Hepacivirus / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D053673:Glypicans; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
keywords: Autophagy; Glypican-3; Hepatocellular carcinoma; Immunostaining; p62