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Precision Medicine and Imaging ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma

Julien Calderaro 1 Léa Meunier 2 Cong Trung Nguyen 1 Marouane Boubaya 3 Stefano Caruso 2 Alain Luciani 4, 5 Giuliana Amaddeo 6, 4 Hélène Regnault 6 Jean-Charles Nault 2, 7 Justine Cohen 8 Frédéric Oberti 9 Sophie Michalak 10 Mohamed Bouattour 11 Valérie Vilgrain 11 Georges Pageaux 12 Jeanne Ramos 13 Nathalie Barget 14 Boris Guiu 15 Valérie Paradis 11 Christophe Aubé Alexis Laurent 16 Jean-Michel Pawlotsky 4 Nathalie Ganne-Carri 2, 14 Jessica Zucman-Rossi 2, 17 Olivier Seror 14 Marianne Ziol 14, 2
Abstract : Purpose: Macrotrabecular-massive hepatocellular carcino-ma (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 immunohis-tochemistry 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 endo-thelial 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 biomar-kers, 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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Julien Calderaro, Léa Meunier, Cong Trung Nguyen, Marouane Boubaya, Stefano Caruso, et al.. Precision Medicine and Imaging ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma. Clin Cancer Res, 2019, 25 (19), pp.5859 - 65. ⟨10.1158/1078-0432.CCR-19-0859⟩. ⟨inserm-02536026⟩

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