Fig. 2.

Pathogenesis of VETC-positive HCCs.

VETC formation is particularly dependent on angiopoietin 2 which is influenced by miR-100, miR-125b, and the androgen receptor. Instead of the traditional EMT pathway for metastasis, VETC-positive HCCs can metastasise in an invasion-independent manner via embolisation of tumour clusters. Ang, angiopoietins; EMT, epithelial mesenchymal transition; FGF, fibroblast growth factor; HCC, hepatocellular carcinoma; mTOR, mammalian target of rapamycin; MVI, microvascular invasion; MTM, macrotrabecular massive; PDGF, platelet-derived growth factor; PD-L1, programmed death-ligand 1; PlGF, placental growth factor; VEGF, vascular endothelial growth factor; VETC, vessels that encapsulate tumour clusters.