MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept

Author:

Gigante Elia12ORCID,Cazier Hélène13,Albuquerque Miguel4ORCID,Laouirem Samira1ORCID,Beaufrère Aurélie14,Paradis Valérie14

Affiliation:

1. Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France

2. Service d’Hépato-Gastroentérologie et Cancérologie Digestive, Hôpital Robert Debré, F-51090 Reims, France

3. Plateforme iMAP, Centre de Recherche sur L'inflammation, Inserm, Université Paris Cité, F-75018 Paris, France

4. Département de Pathologie, Assistance Publique-Hôpitaux de Paris, FHU MOSAIC, Hôpital Beaujon, F-92110 Clichy, France

Abstract

Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference29 articles.

1. New Insights into the Pathophysiology and Clinical Care of Rare Primary Liver Cancers;Gigante;JHEP Rep. Innov. Hepatol.,2021

2. Combined Hepatocellular-Cholangiocarcinoma: An Update;Calderaro;J. Hepatol.,2021

3. (2019). Combined Hepatocellular-Cholangiocarcinoma and Undifferentiated Primary Liver Carcinoma. WHO Classification of Tumours: Digestive System Tumours, IARC. [5th ed.].

4. CHCC-CCA: Consensus Terminology for Primary Liver Carcinomas with Both Hepatocytic and Cholangiocytic Differentation;Brunt;Hepatology,2018

5. Nestin as a Diagnostic and Prognostic Marker for Combined Hepatocellular-Cholangiocarcinoma;Calderaro;J. Hepatol.,2022

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