Tumor budding as a potential prognostic marker in determining the behavior of primary liver cancers

Hepatocellular (HCC) and intrahepatic cholangiocarcinoma (ICC), the most common primary tumors of the liver, are among the most important causes of cancer deaths worldwide. Because patients with primary liver tumors are frequently diagnosed at an advanced stage and have high mortality, many efforts have been made to identify new markers to determine their behavior and treatment, similar to those in other solid organ tumors. Recently, morphological assessment of tumor budding (TB) has been revealed as a promising prognostic finding to predict tumor behavior and survival across several different tumor types. Currently, the TB score in colorectal cancer has been revealed as an important parameter in pathology report protocols to determine the course of the disease. Regarding the liver, despite enormous data showing that many mechanisms involved in TB are associated with tumor behavior in both HCC and ICC, studies focusing on the role of TB in predicting the behavior and prognosis of these tumors have started to be investigated very recently. The purpose of this review is to present data about TB in primary tumors of the liver, pointing out the potential role of this parameter in determining the course of the disease, and emphasize the need to increase the number of further studies focusing on the evaluation of this parameter with an overview of the mechanisms involved in TB.