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Anal Bioanal Chem (2011) 401:17–27 DOI 10.1007/s00216-011-5003-6

REVIEW

MALDI tissue imaging: from biomarker discovery to clinical applications
Lisa H. Cazares & Dean A. Troyer & Binghe Wang & Richard R. Drake & O. John Semmes

Received: 7 January 2011 / Revised: 31 March 2011 / Accepted: 8 April 2011 / Published online: 4 May 2011 # Springer-Verlag 2011

Abstract Matrix-assisted laserdesorption ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for the generation of multidimensional spatial expression maps of biomolecules directly from a tissue section. From a clinical proteomics perspective, this method correlates molecular detail to histopathological changes found in patient-derived tissues, enhancing the ability to identify candidates for diseasebiomarkers. The unbiased analysis and spatial mapping of a variety of molecules directly from clinical tissue sections can be achieved through this method. Conversely, targeted IMS, by the incorporation of laser-reactive molecular tags onto antibodies, aptamers, and other affinity molecules, enables analysis of specific molecules or a class of molecules. In addition to exploring tissue during biomarkerdiscovery, the integration of MALDI-IMS methods into existing clinical pathology laboratory practices could prove beneficial to diagnostics. Querying tissue for the expression of specific biomarkers in a biopsy is a critical component in clinical decision-making and such markers are a major goal of
Published in the special issue MALDI Imaging with Guest Editor Olivier Laprévote. L. H. Cazares : R.R. Drake : O. John Semmes Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA L. H. Cazares : D. A. Troyer : R. R. Drake : O. John Semmes (*) The Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA e-mail: semmesoj@evms.edu B. Wang Department of Chemistry, Georgia State University, Atlanta,GA 30303, USA

translational research. An important challenge in cancer diagnostics will be to assay multiple parameters in a single slide when tissue quantities are limited. The development of multiplexed assays that maximize the yield of information from a small biopsy will help meet a critical challenge to current biomarker research. This review focuses on the use of MALDI-IMS in biomarkerdiscovery and its potential as a clinical diagnostic tool with specific reference to our application of this technology to prostate cancer. Keywords Matrix-assisted laser desorption ionization tissue imaging . Biomarker discovery . Cancer

Introduction Direct analysis of clinical tissues using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) represents a uniqueapproach to assessing spatial expression of molecules linked with histopathology and compiled clinical information. In this regard, MALDI-IMS can be utilized as a biomarker discovery tool as it facilitates a pathology-directed, unbiased approach to identifying the cellular origins and relative concentrations of biomarker candidates across an entire tissue section. MALDI ion sources are well suitedto this application since they enable the ionization of diverse biomolecules, including peptides, proteins, oligonucleotides, sugars, and lipids [1, 2]. Once a marker of interest has been identified, properties related to its localization, abundance, regulation, and function can be assessed across multiple tissues to better understand disease progression at the molecular level. Our group hasapplied MALDI-IMS to the analysis of over 200 individual prostate-tumor-associated tissue samples [3], as well as over 100 tissues related to kidney and bladder cancers.

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From these studies and others, it is clear that issues related to sample manipulation, pathology-directed interrogation, improved and class-specific ionization, and across-class multiplexing present...
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