HCC Part 2: Hepatocarcinogenesis: Molecular & Cellular mechanism

 HCC Part 2: Hepatocarcinogenesis: Molecular & Cellular mechanism

- A process if gradual transformation of non-malignant cells into HCC

- Cell of origin: Mature  Hepatocytes vs Intrahepatic stem cells

- Complex multi-step process

- Chronic inflammation plays a pivotal role due to repeated cycles of cell injury, death and regeneration. 

- The new environment  leads to: 

• Aberrant cell signaling, 
• Epigenetic changes, 
• Mutational events
• Accumulation of genetic damage

- Two phase:

1. Preneoplastic phase (Morphological silent):

• Precedes years & decades before cirrhosis is established
• Runs parallel to fibrosis & cirrhosis
• Molecular aberrant but phenotypically normal
• Few or no structural changes in the genes or chromosomes

2. Neoplastic phase (structural alterations):

• Cells acquire progressive atypical phenotypic features
• Evolve to frank malignancy

Genomic changes are Heterogeneous & diverse

Several molecular variants may be produced with different growth properties in the same liver in different regions. 

Phenotype:

• Hepatocellular phenotype
• Cholangiocellular phenotype
• Combined or mixed features

Prepared by : Dr. Sharad Maheshwari

11.7.2023

Updated: 

Reference: 

https://pubs.rsna.org/doi/pdf/10.1148/radiol.14132361