title: How Suitable is Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight for Metabolite Imaging from Clinical Formalin-Fixed and Paraffin-Embedded Tissue Samples in Comparison to Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry?
abstract: In research and clinical settings, formalin-fixed and paraffin-embedded (FFPE) tissue specimens are collected routinely and therefore this material constitutes a highly valuable source to gather insight in metabolic changes of diseases. Among mass spectrometry techniques to examine the molecular content of FFPE tissue, mass spectrometry imaging (MSI) is the most appropriate when morphological and histological features are to be related to metabolic information. Currently, high-resolution mass spectrometers are widely used for metabolomics studies. However, with regards to matrix-assisted laser desorption/ionization (MALDI) MSI, no study has so far addressed the necessity of instrumental mass resolving power in terms of clinical diagnosis and prognosis using archived FFPE tissue. For this matter we performed for the first time a comprehensive comparison between a high mass resolution Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer and a time-of-flight (TOF) instrument with lower mass resolving power. Spectra analysis revealed that about one-third of the detected peaks remained unresolved by MALDI-TOF, which led to a 3-5 times lower number of m/z features compared to FTICR measurements. Overlaid peak information and background noise in TOF images made a precise assignment of molecular attributes to morphological features more difficult and limited classification approaches. This clearly demonstrates the need for high-mass resolution capabilities for metabolite imaging. Nevertheless, MALDI-TOF allowed reproducing and verifying individual markers identified previously by MALDI-FTICR MSI. The systematic comparison gives rise to a synergistic combination of the different MSI platforms for high-throughput discovery and validation of biomarkers.
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München , Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Buck
authors.affiliation: Maastricht MultiModal Molecular Imaging Institute (M4I), Maastricht University , 6200 MD, Maastricht, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München , Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Voss
authors.affiliation: Institute of Pathology, University of Bern , 3012, Bern, Switzerland.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Zentrum München , 85764, Neuherberg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Zitzelsberger
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München , Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München , Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
mesh_terms: D015415:Biomarkers / Q000032:analysis; D003110:Colonic Neoplasms / Q000401:mortality / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology; D005557:Formaldehyde / Q000737:chemistry; D005583:Fourier Analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D055432:Metabolomics; D016612:Paraffin Embedding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D005557:Formaldehyde