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J Pathol. 2015 Sep;237(1):123-32. doi: 10.1002/path.4560. Epub 2015 Jun 30.

High-resolution MALDI-FT-ICR MS imaging for the analysis of metabolites from formalin-fixed, paraffin-embedded clinical tissue samples.

Author information

1
Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
2
Centre for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
3
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
4
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
5
Institute of Pathology, Technische Universität München, Munich, Germany.
6
Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
7
Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.

Abstract

We present the first analytical approach to demonstrate the in situ imaging of metabolites from formalin-fixed, paraffin-embedded (FFPE) human tissue samples. Using high-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR MSI), we conducted a proof-of-principle experiment comparing metabolite measurements from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst 1700 m/z species. In particular, we observed conservation of biomedically relevant information at the metabolite level in FFPE tissues. In biomedical applications, we analysed tissues from 350 different cancer patients and were able to discriminate between normal and tumour tissues, and different tumours from the same organ, and found an independent prognostic factor for patient survival. This study demonstrates the ability to measure metabolites in FFPE tissues using MALDI-FT-ICR MSI, which can then be assigned to histology and clinical parameters. Our approach is a major technical, histochemical, and clinicopathological advance that highlights the potential for investigating diseases in archived FFPE tissues.

KEYWORDS:

MALDI; cancer; formalin-fixed paraffin-embedded tissue; imaging mass spectrometry; metabolite

PMID:
25965788
DOI:
10.1002/path.4560
[Indexed for MEDLINE]

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