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J Hepatol. 2019 Sep;71(3):616-630. doi: 10.1016/j.jhep.2019.06.001. Epub 2019 Jun 10.

Molecular and histological correlations in liver cancer.

Author information

1
Assistance Publique-Hôpitaux de Paris, Département de Pathologie, CHU Henri Mondor, F-94000 Créteil, France; Université Paris-Est Créteil, Faculté de Médecine, Créteil, France; Inserm U955, Team 18, Créteil, France. Electronic address: julien.calderaro@aphp.fr.
2
INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, 75010 Paris, France; Université Paris 13, Sorbonne Paris-Cité, Bobigny, France; Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et de Cytologie Pathologiques, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, Bondy, France.
3
Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et de Cytologie Pathologiques, Hôpital Universitaire Beaujon, France; Université Paris Diderot, CNRS, Centre de Recherche sur l'Inflammation (CRI), Paris, Département Hospitalo-Universitaire (DHU) UNITY, Clichy, France.
4
INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, 75010 Paris, France; Université Paris Descartes, Université Paris Diderot, Université Paris 13, F-75010, France; Assistance Publique-Hôpitaux de Paris, Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France.

Abstract

Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, both at the molecular and histological level. High-throughput sequencing and gene expression profiling have identified distinct transcriptomic subclasses and numerous recurrent genetic alterations; several HCC subtypes characterised by histological features have also been identified. HCC phenotype appears to be closely related to particular gene mutations, tumour subgroups and/or oncogenic pathways. Non-proliferative tumours display a well-differentiated phenotype. Among this molecular subgroup, CTNNB1-mutated HCCs constitute a homogeneous subtype, exhibiting cholestasis and microtrabecular and pseudoglandular architectural patterns. Another non-proliferative subtype has a gene expression pattern similar to that of mature hepatocytes (G4) and displays a steatohepatitic phenotype. In contrast, proliferative HCCs are most often poorly differentiated, and notably include tumours with progenitor features. A novel morphological variant of proliferative HCC - designated "macrotrabecular-massive" - was recently shown to be associated with angiogenesis activation and poor prognosis. Altogether, these findings may help to translate our knowledge of HCC biology into clinical practice, resulting in improved precision medicine for patients with this highly aggressive malignancy. This manuscript reviews the most recent data in this exciting field, discussing future directions and challenges.

KEYWORDS:

Diagnosis; HCC; Hepatocellular carcinoma; Histology; Mutations; Phenotype; Prognosis; Treatment algorithms

PMID:
31195064
DOI:
10.1016/j.jhep.2019.06.001

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