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- Polyploidy spectrum: a new marker in HCC classification
Polyploidy spectrum: a new marker in HCC classification
Auteurs
Myriam Bou-Nader, Stefano Caruso, Romain Donne, Séverine Celton-Morizur, Julien Calderaro, Géraldine Gentric, Mathilde Cadoux, Antoine L’Hermitte, Christophe Klein, Thomas Guilbert, Miguel Albuquerque, Gabrielle Couchy, Valérie Paradis, Jean-Pierre Couty, Jessica Zucman-Rossi, Chantal Desdouets
Résumé
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
Conclusions
Our results underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.