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International Journal of Legal Medicine

, Volume 132, Issue 6, pp 1675–1684 | Cite as

Multiplex quantitative imaging of human myocardial infarction by mass spectrometry-immunohistochemistry

  • Aleksandra Aljakna
  • Estelle Lauer
  • Sébastien Lenglet
  • Silke Grabherr
  • Tony Fracasso
  • Marc Augsburger
  • Sara Sabatasso
  • Aurélien Thomas
Original Article

Abstract

Simultaneous assessment of a panel of protein markers is becoming essential in order to enhance biomarker research and improve diagnostics. Specifically, postmortem diagnostics of early myocardial ischemia in sudden cardiac death cases could benefit from a multiplex marker assessment in the same tissue section. Current analytical antibody-based techniques (immunohistochemistry and immunofluorescence) limit multiplex analysis usually to not more than three antibodies. In this study, mass spectrometry-immunohistochemistry (MS-IHC) was performed by combining laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) with rare-metal-isotope-tagged antibodies as a technique for multiplex analysis of human postmortem myocardial tissue samples. Tissue sections with myocardial infarction were simultaneously analyzed for seven primary, rare-metal-isotope-tagged antibodies (troponin T, myoglobin, fibronectin, C5b-9, unphosphorylated connexin 43, VEGF-B, and JunB). Comparison between the MS-IHC approach and chromogenic IHC showed similar patterns in ionic and optical images. In addition, absolute quantification was performed by MS-IHC, providing a proportional relationship between the signal intensity and the local marker concentration in tissue sections. These data demonstrated that LA-ICP-MS combined with rare-metal-isotope-tagged antibodies is an efficient strategy for simultaneous testing of multiple markers and allows not only visualization of molecules within the tissue but also quantification of the signal. Such imaging approach has a great potential in both diagnostics and pathology-related research.

Keywords

Mass spectrometry-immunohistochemistry Multiplex tissue imaging Biomarker Myocardial ischemia Forensic pathology 

Notes

Acknowledgements

We would like to thank Max Villa and Catia Pomponio for the support and assistance with LA-ICP-MS and immunohistochemistry, respectively.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

For this type of study, formal consent is not required. All cases included in this study were obtained from the autopsy database in our center. In agreement with the local ethics committee and the local general prosecutor, these cases can be included in this type of studies, provided that they are anonymized. In this investigation, no information allowing the identification of a person is given. People, who had previously refused, in a written form, their consent to bequeath their body parts for research use, were excluded from the study.

Supplementary material

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Supplementary Fig1 (JPEG 732 kb)
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Supplementary Fig2 (JPEG 1653 kb)
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Supplementary Fig3 (JPEG 285 kb)
414_2018_1813_MOESM4_ESM.docx (26 kb)
Table S1 (DOCX 26 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Aleksandra Aljakna
    • 1
  • Estelle Lauer
    • 1
  • Sébastien Lenglet
    • 1
  • Silke Grabherr
    • 1
  • Tony Fracasso
    • 1
  • Marc Augsburger
    • 1
  • Sara Sabatasso
    • 1
  • Aurélien Thomas
    • 1
    • 2
  1. 1.University Center of Legal Medicine, Lausanne-GenevaGenevaSwitzerland
  2. 2.Faculty of Biology and MedicineUniversity of LausanneLausanne 25Switzerland

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