Format

Send to

Choose Destination
Exp Mol Pathol. 2014 Apr;96(2):149-54. doi: 10.1016/j.yexmp.2013.12.002. Epub 2013 Dec 23.

Impaired autophagy response in human hepatocellular carcinoma.

Author information

1
Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
2
The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
3
Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: sdash@tulane.edu.

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.

AIM:

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.

KEYWORDS:

Autophagy; Glypican-3; Hepatocellular carcinoma; Immunostaining; p62

PMID:
24369267
PMCID:
PMC4364514
DOI:
10.1016/j.yexmp.2013.12.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center