Table 1.
Genotype/phenotype classification of hepatocellular adenomas.
| Group | % | Genetic alteration | Pathway dysregulated | mRNA markers | Protein markers | Clinical association | Histological phenotype | |
|---|---|---|---|---|---|---|---|---|
|
HNF1A-mutated HCA |
30–45% | HNF1A | Tumor suppressor gene |
Activation of glycolysis, fatty acid synthesis, and mTor pathway | Decrease LFABP1 UGT2B7 |
lack of LFABP1 expression |
Adenomatosis and association with MODY 3 diabetes (HNF1A germline mutation) | Diffuse steatosis |
|
| ||||||||
|
CTNNB1-mutated HCA* |
10–15% | CTNNB1 | Oncogene | Activation of Wnt/catenin pathway |
Increase GLUL LGR5 |
overexpression of glutamine synthase and nuclear β-catenin |
Risk of malignant transformation Male |
Cell atypia and cholestasis |
|
| ||||||||
| Inflammatory HCA* |
40–55% | IL6ST (65%) | Oncogene | Activation of JAK/STAT pathway (“oncogene-induced inflammation”) |
Increase SAA CRP |
SAA and CRP over-expression |
Obesity and high alcohol intake Inflammatory syndrome |
Inflammatory infiltrate Sinusoidal dilatation Dystrophic arteries |
| STAT3 (6%) | ||||||||
| GNAS (5%) | ||||||||
| Unknown (24%) | ||||||||
|
| ||||||||
| Unclassified | 10% | Unknown | ||||||
*50% of CTNNB1-mutated adenomas are also inflammatory.