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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalProceedings of the Japan Academy Series B: Physical and Biological Sciences
Volume83
Issue number7
DOIs
Publication statusPublished - 2007

Fingerprint

paraffins
formalin
Paraffin
alkanes
Formaldehyde
Mass Spectrometry
Frozen Sections
mass spectroscopy
image analysis
mass spectrometry
biomarkers
Biomarkers
xylene
Xylenes
ovarian neoplasms
mass spectra
methodology
retrospective studies
Ovarian Neoplasms
pharmacokinetics

Keywords

  • Formalin-fixed paraffin embedded
  • Mass spectrometry imaging
  • Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
  • Ovarian cancer

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • General

Cite this

A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging. / Aoki, Yutaka; Toyama, Atsuhiko; Shimada, Takashi; Sugita, Tetsuyoshi; Aoki, Chikage; Umino, Yukari; Suzuki, Atsushi; Aoki, Daisuke; Daigo, Yataro; Nakamura, Yusuke; Sato, Taka Aki.

In: Proceedings of the Japan Academy Series B: Physical and Biological Sciences, Vol. 83, No. 7, 2007, p. 205-214.

Research output: Contribution to journalArticle

Aoki, Yutaka ; Toyama, Atsuhiko ; Shimada, Takashi ; Sugita, Tetsuyoshi ; Aoki, Chikage ; Umino, Yukari ; Suzuki, Atsushi ; Aoki, Daisuke ; Daigo, Yataro ; Nakamura, Yusuke ; Sato, Taka Aki. / A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging. In: Proceedings of the Japan Academy Series B: Physical and Biological Sciences. 2007 ; Vol. 83, No. 7. pp. 205-214.
@article{bed6df1e35494f0daec8aba22fe06c98,
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.",
keywords = "Formalin-fixed paraffin embedded, Mass spectrometry imaging, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Ovarian cancer",
author = "Yutaka Aoki and Atsuhiko Toyama and Takashi Shimada and Tetsuyoshi Sugita and Chikage Aoki and Yukari Umino and Atsushi Suzuki and Daisuke Aoki and Yataro Daigo and Yusuke Nakamura and Sato, {Taka Aki}",
year = "2007",
doi = "10.2183/pjab.83.205",
language = "English",
volume = "83",
pages = "205--214",
journal = "Proceedings of the Japan Academy Series B: Physical and Biological Sciences",
issn = "0386-2208",
publisher = "Japan Academy",
number = "7",

}

TY - JOUR

T1 - A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging

AU - Aoki, Yutaka

AU - Toyama, Atsuhiko

AU - Shimada, Takashi

AU - Sugita, Tetsuyoshi

AU - Aoki, Chikage

AU - Umino, Yukari

AU - Suzuki, Atsushi

AU - Aoki, Daisuke

AU - Daigo, Yataro

AU - Nakamura, Yusuke

AU - Sato, Taka Aki

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - Formalin-fixed paraffin embedded

KW - Mass spectrometry imaging

KW - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

KW - Ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=36049026123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36049026123&partnerID=8YFLogxK

U2 - 10.2183/pjab.83.205

DO - 10.2183/pjab.83.205

M3 - Article

VL - 83

SP - 205

EP - 214

JO - Proceedings of the Japan Academy Series B: Physical and Biological Sciences

JF - Proceedings of the Japan Academy Series B: Physical and Biological Sciences

SN - 0386-2208

IS - 7

ER -