Epithelial-Mesenchymal Transition is Superior to Vessels-Encapsulate Tumor Cluster in Promoting Metastasis of Hepatocellular Carcinoma: a Morphological Evidence

Purpose Vessels-encapsulate tumor cluster (VETC) is a vascular pattern distinct from classical capillary-like pattern. It is reported that VETC structure is common in hepatocellular carcinoma (HCC) and can promote HCC metastasis in an epithelial-mesenchymal transition (EMT)-independent but VETC-dependent manner. However, the main metastatic manner of HCC containing both VETC and classical vascular structure (we called VETC(±)) is unknown. Methods Vascular pattern types and E-cadherin expression were evaluated by immunohistochemical staining in 168 HCC tissues, 50 pairs of primary HCC tissues and intrahepatic metastatic lesions, as well as 12 pairs of primary HCC tissues and major portal vein tumor thrombus. Survival and recurrence rates were evaluated using Kaplan-Meier analysis. The multivariate Cox proportional hazards model was used to determine the independent prognostic factors of HCC. Results VETC(±) cases were more common than VETC(+) cases (HCC tissues with a VETC pattern fully distributed in the HCC section) in HCC. Statistical analysis showed that VETC(±) was an independent predictor of survival and recurrence. Furthermore, E-cadherin was positively correlated with the presence of VETC structure. In the case of HCCs with VETC(±), their metastases (both intrahepatic and major vascular) were more likely to be VETC negative. Conclusions Our findings suggest that EMT may be superior to VETC in promoting HCC metastasis. Thus, both anti-EMT and anti-VETC agents should be considered in the case of HCC with VETC(±).