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Review
. 2022 Jul 7;28(25):2854-2866.
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  1 , Antonio De Leo  1 , Viviana Sanza  2 , Elisa Gruppioni  2 , Annalisa Altimari  2 , Mattia Riefolo  3 , Michela Visani  1 , Deborah Malvi  3 , Antonia D'Errico  3 , Giovanni Tallini  1 , Francesco Vasuri  3 , Dario de Biase  4
Affiliations
Review

Correlation of molecular alterations with pathological features in hepatocellular carcinoma: Literature review and experience of an Italian center

Thais Maloberti et al. World J Gastroenterol. .

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: CTNNB1; Hepatocarcinoma; Mutation; Next-generation sequencing; Review; TERT; TP53.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Main cellular pathways and clinical implications of TERT mutations in hepatocellular carcinoma. Created with BioRender.com. HBV: Hepatitis B virus; HCV: Hepatitis C virus.
Figure 2
Figure 2
Main cellular pathways and clinical implications of CTNNB1 mutations in hepatocellular carcinoma. Created with BioRender.com. APC: Adenomatous polyposis coli; DSH: Disheveled; GSK: Glycogen synthase kinase; HCV: Hepatitis C virus; LEF: Lymphoid enhancing factor; TCF: T-cell factor.
Figure 3
Figure 3
Main cellular pathways and clinical implications of TP53 mutations in hepatocellular carcinoma. Created with BioRender.com. HBV: Hepatitis B virus.
Figure 4
Figure 4
Steatohepatitic hepatocellular carcinomas and clear cell carcinoma and their molecular features. Hematoxylin-eosin stain ( 10 magnification). HCC: Hepatocellular carcinoma.
Figure 5
Figure 5
Macrotrabecular massive hepatocellular carcinomas and scirrhous hepatocellular carcinoma and their molecular features. Hematoxylin-eosin stain ( 10 magnification). HCC: Hepatocellular carcinoma; TGF: Transforming growth factor.
Figure 6
Figure 6
Representation of our data based on the number of samples grouped according to their mutational status.
Figure 7
Figure 7
A case from our series of high-grade (Edmondson’s 4) hepatocellular carcinoma, with tumor giant cells and macrotrabecular architecture. Left boxes: coexistent TERT and TP53 mutations detected by next-generation sequencing analysis; Right boxes: Hematoxylin-eosin stain ( 10 and 20 magnification). HCC: Hepatocellular carcinoma.
See this image and copyright information in PMC

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