Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2016; 22(14): 3735-3745
Published online Apr 14, 2016. doi: 10.3748/wjg.v22.i14.3735
Phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease
Andrea Sanchez-Pareja, Sophie Clément, Marion Peyrou, Laurent Spahr, Francesco Negro, Laura Rubbia-Brandt, Michelangelo Foti
Andrea Sanchez-Pareja, Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Division of Clinical Pathology, University Hospital of Geneva, 1211 Geneva, Switzerland
Marion Peyrou, Michelangelo Foti, Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Marion Peyrou, Michelangelo Foti, Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
Laurent Spahr, Francesco Negro, Division of Gastroenterology and Hepatology, University Hospital of Geneva, 1211 Geneva, Switzerland
Author contributions: Rubbia-Brandt L and Foti M contributed equally to this work; Sanchez-Pareja A and Clément S acquired the data; Sanchez-Pareja A, Clément S, Peyrou M, Negro F, Rubbia-Brandt L and Foti M analyzed and interpreted the data; Spahr L and Rubbia-Brandt L provided material; Sanchez-Pareja A, Clément S and Foti M wrote the manuscript; Peyrou M, Spahr L, Negro F, Rubbia-Brandt L and Foti M critically revised the manuscript for important intellectual content; Rubbia-Brandt L and Foti M designed the study; Negro F and Foti M obtained funding.
Supported by the Swiss National Science Foundation, No. 314730-146991 (to Negro F); and the Swiss National Science Foundation, No. 310030-152618 and No. CRSII3-160717 (to Foti M).
Institutional review board statement: This work was approved by the Ethics Committee of the Geneva University Hospital, Geneva, Switzerland.
Institutional animal care and use committee statement: No animal experimentation was performed in this work.
Conflict-of-interest statement: None related to the content of this article.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Michelangelo Foti, Professor, Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Centre Médical Universitaire, 1 rue Michel-Servet, 1211 Geneva, Switzerland. michelangelo.foti@unige.ch
Telephone: +41-22-3795204 Fax: +41-22-3795260
Received: December 21, 2015
Peer-review started: December 22, 2015
First decision: January 13, 2016
Revised: January 28, 2016
Accepted: March 1, 2016
Article in press: March 2, 2016
Published online: April 14, 2016
Processing time: 98 Days and 20.5 Hours
Abstract

AIM: 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).

CONCLUSION: 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.

Keywords: Fibrosis; Phosphatase and tensin homolog; Steatosis; Non-alcoholic fatty liver disease; Nonalcoholic steatohepatitis; Alcoholic liver disease; Cirrhosis; Hepatocellular carcinoma

Core tip: Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) display similar histopathological features making difficult to discriminate between them apart from patient history. In this report, we assessed the phosphatase and tensin homolog (PTEN) expression level by immunohistochemistry and observed that while PTEN was downregulated in steatotic hepatocytes from patients with NAFLD, its expression remained unchanged in patients with ALD. We therefore propose that the evaluation of PTEN expression could be a useful tool for the differential diagnosis of NAFLD and ALD.