Clinical, Histological, and Molecular Classification of Hepatocellular Carcinoma: How Do They Get Along?

Abstract

Hepatocellular carcinoma (HCC) will soon become a prominent part of the medical and economic burden on many Western countries’ healthcare systems. This review will discuss some emerging scenarios concerning the different classifications of HCC from the clinical, histological, and molecular perspective and to what extent they are integrated with each other. Beginning with an overview of the current numbers and facts regarding HCC, it touches upon the latest development of the epidemiological scenario. It is noteworthy that besides viral hepatitis infection, the fast growing rate of individuals affected by metabolic syndromes represents an additional influential factor on the rising incidence of HCC. However, despite recognised epidemiological evidence, too little is known about the molecular mechanisms that favour HCC development and progression. For instance, long non-coding RNAs playing a major role in the HCC carcinogenesis process have only recently been recognised. Although high cure rates are achieved for clinically asymptomatic patients when small tumours are detected, HCC is typically silent with few severe symptoms until its advanced stages. Patients with severe clinical signs are seldom good candidates for any type of curative therapy. Microscopically, HCC cells resemble normal liver cells to a variable degree, depending on the tumour differentiation status. Pathologists often use a panel of markers to assist HCC differential diagnosis. From a molecular perspective, HCC presents as a highly heterogeneous tumour entity. Despite considerable research efforts, to date no molecular classification has been introduced in clinical practice. A number of classifications have been suggested to stratify HCC patients by the likelihood of survival, with the aim of identifying those with the best chance of being successfully treated. These different systems do not seem to work well in conjunction and the various involved disciplines have so far failed to achieve their common goal. Co-ordinated initiatives involving clinicians, pathologists, biologists, and bioinformaticians are needed to achieve a comprehensive classification of HCC.