title: Phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease.
abstract: OBJECTIVE
  To investigate the protein expression of phosphatase and tensin homolog (PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.
  
  
  METHODS
  PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffin-embedded liver sections of patients with non-alcoholic fatty liver disease (NAFLD) (n = 44) or alcoholic liver disease (ALD) (n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients' clinical history.
  
  
  RESULTS
  In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis (r = 0.3061, P = 0.0459) and the BMI (r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor (P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients (P < 0.0001).
  
  
  CONCLUSIONS
  PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD.
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sanchez-Pareja
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Marion
authors.initials: M
authors.lastname: Peyrou
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Spahr
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.affiliation: Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Foti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D015536:Down-Regulation; D005235:Fatty Liver, Alcoholic / Q000175:diagnosis* / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000201:enzymology; D015588:Observer Variation; D051059:PTEN Phosphohydrolase / Q000097:blood*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Alcoholic liver disease; Cirrhosis; Fibrosis; Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Nonalcoholic steatohepatitis; Phosphatase and tensin homolog; Steatosis