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
References
Oct 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M RoncalliM Borzio
Jun 15, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Luigi BolondiFabio Piscaglia
Feb 7, 2007·Cancer·Young Nyun ParkMassimo Roncalli
Feb 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Luca Di TommasoMassimo Roncalli
Feb 28, 2008·The American Journal of Surgical Pathology·Wanda M P CostonPeiguo G Chu
Jan 30, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·UNKNOWN International Consensus Group for Hepatocellular NeoplasiaThe International Consensus Group for Hepatocellular Neoplasia
Feb 24, 2009·Journal of Hepatology·Luca Di TommasoMassimo Roncalli
Jun 6, 2009·Cancer Science·Hirofumi ShirakawaTetsuya Nakatsura
Feb 19, 2011·Gut·Mu-Yan CaiDan Xie
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Luca Di TommasoMassimo Roncalli
Jan 31, 2012·Gut·Silvia TremosiniJordi Bruix
Oct 16, 2012·Journal of Hepatology·Yutaka MidorikawaMasatoshi Tanaka
Dec 13, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Emmanuel TsochatzisAndrew K Burroughs
Mar 28, 2013·Journal of Gastroenterology·I-Pei ChenMasakazu Yamamoto
Jul 3, 2013·Best Practice & Research. Clinical Gastroenterology·Luca Di TommasoMassimo Roncalli
Jul 28, 2013·Nature Communications·Jean Charles NaultJessica Zucman Rossi
Jun 20, 2014·Liver Cancer·Tomoaki IchikawaHiroyuki Morisaka
Aug 16, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jean Charles NaultJessica Zucman-Rossi
Nov 5, 2014·Seminars in Liver Disease·Roser PinyolJosep M Llovet
Apr 14, 2015·Liver International : Official Journal of the International Association for the Study of the Liver·Amedeo SciarraValérie Paradis
Citations
Apr 17, 2016·Journal of Hepatology·Massimo Levrero, Jessica Zucman-Rossi
Apr 15, 2016·Digestive Diseases and Sciences·Guijuan ZongXudong Chen
Oct 25, 2016·Journal of Medical Ultrasonics·Kazuya SugimoriKatsuaki Tanaka
May 24, 2018·Histopathology·Noemi RudiniLuca Di Tommaso
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
Jan 6, 2019·Journal of Clinical Pathology·Dingbao ChenJi-Ye Zhu
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
Nov 21, 2017·Oncotarget·Long-Hai FengWen-Ming Cong
Sep 15, 2016·Gut·Timothy Hardy, Derek A Mann
Sep 8, 2017·Histopathology·Francesco VasuriAntonia D'Errico
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
May 23, 2020·Diagnostics·Feiqian WangShin Maeda
Apr 8, 2021·British Journal of Cancer·Shi-Xun LuJing-Ping Yun
Apr 17, 2021·European Radiology·Chunli KongJiansong Ji
May 14, 2021·Journal of Hepatocellular Carcinoma·Yanfen FanChunhong Hu
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
May 25, 2021·The Journal of Pathology·Waleed FateenPhilip Quirke