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World J Gastroenterol. Jul 7, 2022; 28(25): 2854-2866
Published online Jul 7, 2022. doi: 10.3748/wjg.v28.i25.2854
Correlation of molecular alterations with pathological features in hepatocellular carcinoma: Literature review and experience of an Italian center
Thais Maloberti, Antonio De Leo, Viviana Sanza, Elisa Gruppioni, Annalisa Altimari, Mattia Riefolo, Michela Visani, Deborah Malvi, Antonia D’Errico, Giovanni Tallini, Francesco Vasuri, Dario de Biase
Thais Maloberti, Antonio De Leo, Michela Visani, Giovanni Tallini, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
Thais Maloberti, Antonio De Leo, Viviana Sanza, Elisa Gruppioni, Annalisa Altimari, Giovanni Tallini, Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
Mattia Riefolo, Deborah Malvi, Antonia D’Errico, Francesco Vasuri, Department of Pathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
Dario de Biase, Department of Pharmacy and biotechnology (FaBiT), University of Bologna, Bologna 40138, Italy
Author contributions: Vasuri F and de Biase D contributed equally to this paper; Maloberti T and Vasuri F designed the research study; Maloberti T, De Leo A, Sanza V, Gruppioni E, Altimari A, Riefolo M, Visani M, and Malvi D performed the research; Maloberti T and Vasuri F analyzed the data and wrote the manuscript; D’Errico A, Tallini G, and de Biase D supervised the manuscript preparation; All authors have read and approved the final manuscript.
Conflict-of-interest statement: Dario de Biase has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim and Eli Lilly, unrelated to the current work.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dario de Biase, MSc, PhD, Associate Professor, Department of Pharmacy and biotechnology (FaBiT), University of Bologna, Viale Ercolani 4/2, S. Orsola Hospital, Bologna 40138, Italy. dario.debiase@unibo.it
Received: January 14, 2022
Peer-review started: January 14, 2022
First decision: March 9, 2022
Revised: March 23, 2022
Accepted: May 27, 2022
Article in press: May 27, 2022
Published online: July 7, 2022
Abstract

Hepatocellular carcinoma (HCC) represents the primary carcinoma of the liver and the fourth leading cause of cancer-related deaths. The World Health Organization estimates an increase in cases in the coming years. The risk factors of HCC are multiple, and the incidence in different countries is closely related to the different risk factors to which the population is exposed. The molecular mechanisms that drive HCC tumorigenesis are extremely complex, but understanding this multistep process is essential for the identification of diagnostic, prognostic, and therapeutic markers. The development of multigenic next-generation sequencing panels through the parallel analysis of multiple markers can provide a landscape of the genomic status of the tumor. Considering the literature and our preliminary data based on 36 HCCs, the most frequently altered genes in HCCs are TERT, CTNNB1, and TP53. Over the years, many groups have attempted to classify HCCs on a molecular basis, but a univocal classification has never been achieved. Nevertheless, statistically significant correlations have been found in HCCs between the molecular signature and morphologic features, and this leads us to think that it would be desirable to integrate the approach between anatomic pathology and molecular laboratories.

Keywords: Hepatocarcinoma, Mutation, Next-generation sequencing, Review, TP53, CTNNB1, TERT

Core Tip: The molecular mechanisms that drive hepatocellular carcinoma tumorigenesis are extremely complex, and a univocal classification based on molecular features has not been defined. In the age of precision medicine, the study of hepatocellular carcinoma mutations is still a field worth investigating. Based on this, we wanted to analyze the possible correlations between molecular alterations and pathological features. Considering both the literature data and our personal experience, about 80% of hepatocellular carcinomas harbor mutations in at least one of the following genes, TERT, TP53, or CTNNB1, with different biological and clinical implications.