Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice

Abstract

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver cancers, accounting for approximately 80% and 15%, respectively. HCC carcinogenesis occurs mostly in cirrhosis and is a complex multi-step process, from precancerous lesions (low-grade and high-grade dysplastic nodules) to progressed HCC.During the different stages of liver carcinogenesis, there is an accumulation of pathological, genetic and epigenetic changes leading to initiation, malignant transformation and finally tumour progression. In contrast, a small subset of HCC occurs in normal liver from the transformation of hepatocellular adenoma (HCA), a benign hepatocellular tumour. The recent molecular classification enables to stratify HCAs according to their risk of complication, in particular malignant transformation, associated with mutations in exon 3 of the catenin beta 1 (CTNNB1) gene. Cholangiocarcinoma (CCA) derives from the multistep malignant transformation of preneoplastic lesions, like biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB), for which a pre-operative diagnosis remains difficult. Different genetic alterations are involved in BilIN and IPNB progression, leading to the development of tubular or intestinal adenocarcinoma. The aims of this review are to describe the main clinical and molecular features of preneoplastic lesions leading to the development of HCC and CCA, their implications in clinical practice and the perspectives for future research.

Clinical validation of a next-generation sequencing-based multi-cancer early detection “liquid biopsy” blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study

“…First, in the context of the above considerations, the absence of malignancy could not be ascertained in such cases, so they could be used for neither the calculation of sensitivity (which required cancer-diagnosed subjects) nor the calculation of specificity (which required subjects without a diagnosis or a suspicion of cancer). Second, it has been established in human oncology that patients with a history of benign masses have an elevated relative risk of malignancy in multiple organs, such as breast [ 97 , 98 ], uterus [ 99 ], colon [ 100 ], and liver [ 101 , 102 ]. For perspective, two recent large clinical validation studies for MCED tests intended for use in humans also excluded potentially confounding cases (such as those with high-grade dysplasia or with suspected but unconfirmed cancer status at the time of blood collection) from their analysis, and neither study provided an analysis of subjects with benign tumors [ 50 , 51 ].…”

DDX39B facilitates the malignant progression of hepatocellular carcinoma via activation of SREBP1-mediated de novo lipid synthesis

“…The malignant development of HCC is a complicated biological process, including hyperproliferation of tumor cells in situ, remodeling and degradation of the extracellular matrix, stromal and vascular invasion, resistance to anoikis and distant metastasis [30,31] . Identifying novel and effective biomarkers will improve current therapeutic strategies for HCC and prolong the survival of patients with HCC.…”

Current Concepts of Precancerous Lesions of Hepatocellular Carcinoma: Recent Progress in Diagnosis

“…However, the low prevalence of these mutations in DN suggests that they play a more critical role in tumor progression in cirrhosis than in the onset of carcinogenesis [ 28 , 29 ]. Chromosomal alterations, such as copy number variants, have been described in precancerous lesions, mainly including increases or deletions of chromosome 8 arms (8p or 8q) and increases in 1q [ 30 ]. An analysis of the prevalence of SCNAs at the arm level showed that 1q+ and 8q+ were common in HCC, uncommon in DN, and least common in cirrhosis [ 31 , 32 ].…”