title: A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging.
abstract: Significant advances have been made in the past decade in the field of mass spectrometry imaging (MS imaging). It is a relatively unestablished technique aimed at direct, high-sensitive and spatially exclusive detection of biological molecules from the surface of tissue sections, so that semi-quantitative distribution map of the analyte can be reconstituted from the mass spectra obtained. There is tremendous potential in its application especially in clinical field, such as biomarker discovery or pharmacokinetic study. However, vast majority of the work has been performed on frozen tissue sections, while it remains generally unpractical to produce frozen sections with clinically resected tumor samples. Here we report our novel sample preparation technique that enabled MS imaging from formalin-fixed paraffin embedded (FFPE) tissue section, including retrospective archive as old as 11 years. FFPE sections were first dewaxed with pre-warmed xylene, and exposed tissue surface was enzymatically digested in nanoliter scale droplets to retain analyte localization. As a result, we succeeded in obtaining MS images of peptide peaks derived from several proteins, identified by MS/MS analysis, using ovarian cancer FFPE sections. The qualities of mass spectra obtained by this method were not significantly different from those obtained from frozen sections. By this, we opened the door to retrospective study of past clinical cases in aim to discover molecular biomarker.
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Toyama
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Tetsuyoshi
authors.initials: T
authors.lastname: Sugita
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Chikage
authors.initials: C
authors.lastname: Aoki
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Yukari
authors.initials: Y
authors.lastname: Umino
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan .
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan .
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.affiliation: Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan . ; Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan .
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Sato
keywords: formalin-fixed paraffin embedded; mass spectrometry imaging; matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; ovarian cancer