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Gut. 2019 Apr 12. pii: gutjnl-2018-318021. doi: 10.1136/gutjnl-2018-318021. [Epub ahead of print]

Polyploidy spectrum: a new marker in HCC classification.

Author information

1
Team Proliferation Stress and Liver Physiopathology, Genome and Cancer, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Paris, France.
2
Team Functional Genomics of Solid Tumors, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Équipe Labellisée Ligue Contre le Cancer, Paris, France.
3
INSERM U1162, Paris, France.
4
Department of Pathology, Hopital Henri Mondor, Creteil, France.
5
Stress and Cancer Laboratory, Équipe Labelisée LNCC, Institut Curie, Paris, France.
6
INSERM U830, Paris, France.
7
Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
8
INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Paris, France.
9
Institut Cochin, Paris, France.
10
Department of Pathology, Beaujon Hospital, Clichy, France.
11
Hopital Beaujon, Clichy, France.
#
Contributed equally

Abstract

OBJECTIVES:

Polyploidy is a fascinating characteristic of liver parenchyma. Hepatocyte polyploidy depends on the DNA content of each nucleus (nuclear ploidy) and the number of nuclei per cell (cellular ploidy). Which role can be assigned to polyploidy during human hepatocellular carcinoma (HCC) development is still an open question. Here, we investigated whether a specific ploidy spectrum is associated with clinical and molecular features of HCC.

DESIGN:

Ploidy spectra were determined on surgically resected tissues from patients with HCC as well as healthy control tissues. To define ploidy profiles, a quantitative and qualitative in situ imaging approach was used on paraffin tissue liver sections.

RESULTS:

We first demonstrated that polyploid hepatocytes are the major components of human liver parenchyma, polyploidy being mainly cellular (binuclear hepatocytes). Across liver lobules, polyploid hepatocytes do not exhibit a specific zonation pattern. During liver tumorigenesis, cellular ploidy is drastically reduced; binuclear polyploid hepatocytes are barely present in HCC tumours. Remarkably, nuclear ploidy is specifically amplified in HCC tumours. In fact, nuclear ploidy is amplified in HCCs harbouring a low degree of differentiation and TP53 mutations. Finally, our results demonstrated that highly polyploid tumours are associated with a poor prognosis.

CONCLUSIONS:

Our results underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.

KEYWORDS:

cell cycle; hepatocellular carcinoma; histopathology; liver; molecular pathology

PMID:
30979717
DOI:
10.1136/gutjnl-2018-318021
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Conflict of interest statement

Competing interests: None declared.

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