A 58-year-old man with Child-Pugh class B cirrhosis due to chronic hepatitis C has a rising serum AFP and a 3 cm arterially enhancing hepatic mass with portal-phase washout on CT. Core needle biopsy shows trabeculae of malignant hepatocytes without bile duct structures. Which molecular pathway is most commonly altered in hepatocellular carcinoma?
- A Wnt/β-catenin and TP53 pathways ✓
- B RAS-MAPK pathway via KRAS mutation
- C ALK rearrangement
- D HER2 amplification
Correct answer: A. Wnt/β-catenin and TP53 pathways
Explanation
Hepatocellular carcinoma most commonly involves activation of the Wnt/β-catenin pathway (via CTNNB1 mutations) and inactivation of the TP53 tumor suppressor. In HBV-related HCC, HBx protein integrates into the host genome and activates oncogenic pathways including p53 inactivation. In aflatoxin B1-related HCC, a characteristic TP53 mutation at codon 249 (arginine to serine) is the molecular fingerprint of this carcinogen. AFP elevation and arterial enhancement with washout are the radiological hallmarks used in BCLC staging.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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