Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications

Journal of Hepatology
Amedeo SciarraMassimo Roncalli

Abstract

Human hepatocarcinogenesis in cirrhosis is thought to be multistep and characterized by a spectrum of nodular lesions, ranging from low to high grade dysplastic nodules (LGDN and HGDN) to early and progressed hepatocellular carcinoma (eHCC and pHCC). The aim of this study was to investigate the morphophenotypical changes of this sequence and their potential translational significance. We scored the vascular profile, ductular reaction/stromal invasion and overexpression of five biomarkers (GPC3, HSP70, GS, CHC, and EZH2), in a series of 100 resected nodules (13 LGDN, 16 HGDN, 42 eHCC and 29 small pHCC). The score separated the four groups of nodules as individual entities (p<0.01). In the sequence, biomarker's overexpression progressively increased with parallel decrease of ductular reaction; the vascular remodeling started very early (LGDN) but did not further develop in a proportion of HCC. eHCC was the most heterogeneous entity, with marginal overlap with HGDN and pHCC. Liver environment (fibrosis, etiology) did not impact on the phenotype of the different nodules. A subclass of eHCC (16/42) without evidence of stromal invasion was identified, suggesting a "preinvasive stage" (p<0.05). For diagnosis, the application of four a...Continue Reading

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Citations

Apr 17, 2016·Journal of Hepatology·Massimo Levrero, Jessica Zucman-Rossi
Apr 15, 2016·Digestive Diseases and Sciences·Guijuan ZongXudong Chen
Oct 5, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A VogelUNKNOWN ESMO Guidelines Committee
May 4, 2017·ACG Case Reports Journal·Seitarou ShimadaToshiro Sugiyama
Jun 18, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Salvatore Lorenzo RenneLuca Di Tommaso
Oct 28, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Peng LiuXiao Xu
Sep 15, 2016·Gut·Timothy Hardy, Derek A Mann
Jan 18, 2020·Journal of Medical Ultrasonics·Feiqian WangShin Maeda
Oct 14, 2017·Pathology International·Koichi TsuneyamaHirohisa Ogawa
Jul 12, 2018·Nucleic Acids Research·Ying-Ying LeeAlfred S L Cheng
Oct 1, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A VogelUNKNOWN ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org

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