title: High-resolution MALDI-FT-ICR MS imaging for the analysis of metabolites from formalin-fixed, paraffin-embedded clinical tissue samples.
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.
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Buck
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Ly
authors.affiliation: Centre for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Gorzolka
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Janssen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Weirich
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Erlmeier
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aubele
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Zitzelsberger
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D016000:Cluster Analysis; D019295:Computational Biology; D017357:Cyclotrons; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D005404:Fixatives / Q000737:chemistry*; D005557:Formaldehyde / Q000737:chemistry*; D005583:Fourier Analysis; D005858:Germany; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009426:Netherlands; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013997:Time Factors; D016707:Tissue Fixation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005404:Fixatives; D005557:Formaldehyde
keywords: MALDI; cancer; formalin-fixed paraffin-embedded tissue; imaging mass spectrometry; metabolite