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Clin Cancer Res. 2019 Jul 29. doi: 10.1158/1078-0432.CCR-19-0859. [Epub ahead of print]

ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma.

Author information

1
Assistance Publique-Hôpitaux de Paris, Département Pathologie, CHU Henri Mondor, F-94000 Créteil, France. julien.calderaro@aphp.fr.
2
Université Paris-Est Créteil, Faculté de Médecine, Créteil, France.
3
Inserm, U955, Team 18, Créteil, France.
4
INSERM UMR-1162, génomique fonctionnelle des tumeurs solides, Paris, France.
5
Unité de Recherche Clinique, AP-HP, Hôpital Universitaire Avicenne, Bobigny, France.
6
Assistance Publique-Hôpitaux de Paris, Service de Radiologie, CHU Henri Mondor, F-94000 Créteil, France.
7
Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, CHU Henri Mondor, F-94000 Créteil, France.
8
Service d'Hépatologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, AP-HP, Bondy, France.
9
Université Paris 13, Sorbonne Paris-Cité, Bobigny, France.
10
Assistance Publique-Hôpitaux de Paris, Département Pathologie, CHU Henri Mondor, F-94000 Créteil, France.
11
Hépato-gastroentérologie et oncologie digestive, Centre Hospitalier Universitaire d'Angers, France.
12
Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Universitaire d'Angers, France.
13
Assistance Publique-Hôpitaux de Paris, Service d'Oncologie Digestive, Hôpital Universitaire Beaujon, France.
14
Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et de Cytologie Pathologiques, Hôpital Universitaire Beaujon, France.
15
Hépato-gastroentérologie et oncologie digestive, Centre Hospitalier Universitaire de Montpellier, France.
16
Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Universitaire de Montpellier, France.
17
Assistance Publique-Hôpitaux de Paris, Centre de ressources biologiques BB-0033-00027 du Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, Bondy, France.
18
Service de Radiologie, Centre Hospitalier Universitaire de Montpellier, France.
19
Assistance Publique-Hôpitaux de Paris, Service de Radiologie, Hôpital Universitaire Beaujon, France.
20
Service de Radiologie, Centre Hospitalier Universitaire d'Angers, France.
21
Assistance Publique-Hôpitaux de Paris, Département de Chirurgie Digestive et Hépato-Biliaire, CHU Henri Mondor, F-94000 Créteil, France.
22
Service de Virologie, Bactériologie-Hygiène, Mycologie-Parasitologie et Unité Transversale de Traitement des Infections, Assistance-Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Créteil, France.
23
Université Paris Descartes, Université Paris Diderot, Université Paris 13, F-75010, France.
24
Assistance Publique-Hôpitaux de Paris, Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France.
25
Service de Radiologie, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, AP-HP, Bondy, France.
26
Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et de Cytologie Pathologiques, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, Bondy, France.

Abstract

Purpose: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice.Experimental design: To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples.Results: Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76).Conclusions: Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice.

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