Primary Liver Cancers, Part 2: Progression Pathways and Carcinogenesis

Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified. Mutations in catenin beta 1 (CTNBB1) and tumor protein 53 (P53) are the main genetic alterations in HCC. Isocitrate dehydrogenases 1 and 2 (IDH1/2), KRAS protooncogene GTPase (KRAS), a RAS Viral Oncogene Homolog in neoroblastoma (NRAS) and P53 are primary genetic alterations in ICC. In both diseases, the mutational landscape is dependent on the underlying etiology. The most significant etiologies and genetic processes involved in the carcinogenesis of HCC and ICC are reviewed.