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: 

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