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Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging mass spectrometry
Author(s) -
Le Faouder Julie,
Laouirem Samira,
Alexandrov Theodore,
BenHarzallah Soundes,
Léger Thibaut,
Albuquerque Miguel,
Bedossa Pierre,
Paradis Valérie
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300463
Subject(s) - maldi imaging , stromal cell , proteomics , mass spectrometry imaging , mass spectrometry , malignancy , immunohistochemistry , proteome , chemistry , pathology , microbiology and biotechnology , biology , matrix assisted laser desorption/ionization , medicine , biochemistry , chromatography , organic chemistry , adsorption , desorption , gene
Cholangiocarcinoma ( CC ) is the second most common primary malignancy of the liver. Although all CC derive from biliary epithelial cells, two main subtypes, hilar ( H ), and peripheral ( P ) CC are described. The objective of the study was to compare, using MALDI imaging mass spectrometry ( MALDI IMS ), in situ proteomic profiles of H ‐ and P ‐ CC in order to assess whether these subtypes may express different markers and to describe their respective localizations. Twenty‐seven CC (16 P ‐ CC and 11 H ‐ CC ) were subjected to MALDI IMS . Proteomic data were submitted to a dedicated cross‐classification comparative design, enabling comparison of the entire generated spectra. Immunohistochemistry was performed for validation. Comparative analysis yielded a list of 19 differential protein peaks for the two subtypes, 14 of which were overexpressed in H ‐ CC and five in P ‐ CC . Among H ‐ CC protein markers, most discriminant were human neutrophil peptides 1–3 that were expressed mainly by tumor cells and S 100 proteins ( A 6 and A 11) that were restricted to the stromal area. In P ‐ CC , thymosin β4 was diffusely overexpressed. These results highlight the potential of MALDI IMS to discover new relevant biomarkers of CC and to characterize the heterogeneity of the two different subtypes.