A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging

Yutaka AOKI; Atsuhiko TOYAMA; Takashi SHIMADA; Tetsuyoshi SUGITA; Chikage AOKI; Yukari UMINO; Atsushi SUZUKI; Daisuke AOKI; Yataro DAIGO; Yusuke NAKAMURA; Taka-Aki SATO

doi:10.2183/pjab.83.205

Original Papers

A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging

Yutaka AOKI, Atsuhiko TOYAMA, Takashi SHIMADA, Tetsuyoshi SUGITA, Chikage AOKI, Yukari UMINO, Atsushi SUZUKI, Daisuke AOKI, Yataro DAIGO, Yusuke NAKAMURA, Taka-Aki SATO

Author information

Yutaka AOKI
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Atsuhiko TOYAMA
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Takashi SHIMADA
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Tetsuyoshi SUGITA
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Chikage AOKI
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Yukari UMINO
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Atsushi SUZUKI
Department of Obstetrics and Gynecology, Keio University School of Medicine
Daisuke AOKI
Department of Obstetrics and Gynecology, Keio University School of Medicine
Yataro DAIGO
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo
Yusuke NAKAMURA
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
Taka-Aki SATO
Life Science Laboratory, Shimadzu Corporation
Division of Advanced Clinical Proteomics, Institute of Medical Science, University of Tokyo

Keywords: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, mass spectrometry imaging, formalin-fixed paraffin embedded, ovarian cancer

JOURNAL FREE ACCESS

2007 Volume 83 Issue 7 Pages 205-214

DOI https://doi.org/10.2183/pjab.83.205

Details

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.

(Communicated by Koichi TANAKA, M.J.A.)

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