Multiplexed ion beam imaging of human breast tumors
Open accessAbstract
Immunohistochemistry (IHC) is a tool for visualizing protein expression that is employed as part of the diagnostic workup for the majority of solid tissue malignancies. Existing IHC methods use antibodies tagged with fluorophores or enzyme reporters that generate colored pigments. Because these reporters exhibit spectral and spatial overlap when used simultaneously, multiplexed IHC is not routinely used in clinical settings. We have developed a method that uses secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental metal reporters. Multiplexed ion beam imaging (MIBI) is capable of analyzing up to 100 targets simultaneously over a five-log dynamic range. Here, we used MIBI to analyze formalin-fixed, paraffin-embedded human breast tumor tissue sections stained with ten labels simultaneously. The resulting data suggest that MIBI can provide new insights into disease pathogenesis that will be valuable for basic research, drug discovery and clinical diagnostics.
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At least two platforms now allow high-dimensional tissue imaging with antibodies, detecting over 40 parameters in a single section.
“There are now at least two platforms that enable high-dimensional tissue imaging with antibodies, allowing over 40 parameters to be simultaneously detected in a single section (Angelo et al., 2014; Giesen et al., 2014).”
From Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens (2018) · cites this paper as Angelo et al., 2014
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- Authors
- Angelo, M., Bendall, S. C., Finck, R., Hale, M. B., Hitzman, C., Borowsky, A. D., Levenson, R. M., Lowe, J. B., Liu, S. D., Zhao, S., Natkunam, Y., & Nolan, G. P.
- Affiliations
- University of California, San Francisco (US)
- Stanford University (US)
- University of California Davis Medical Center (US)
- Genentech (US)
- Stanford Medicine (US)
- Corresponding author
- Nolan, Garry P
- ORCID
- Venue
- Nature Medicine
- Published
- 2014-03-02
- Volume
- 20
- Issue
- 4
- Pages
- 436-442
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4110905
- OpenAlex
- W2043565262
- Cited by
- 1,108
- References
- 34
- Citations by year
- 2026: 88 · 2025: 86 · 2024: 121 · 2023: 122 · 2022: 114 · 2021: 147 · 2020: 92 · 2019: 89 · 2018: 75 · 2017: 59 · 2016: 53 · 2015: 41 · 2014: 19
- FWCI
- 24.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (0922648, AI057229)
- U.S. Department of Defense
- California Institute for Regenerative Medicine (RB2-01592, DR1-01477)
- Damon Runyon Cancer Research Foundation (DRG-2017-09)
- European Commission
- National Institutes of Health (1s10od016318-01, N01-HV-00242, 5u54ca143907-05, HHSN272200700038C, n01hv28183-13-0-0, 5U54 CA143907, AI057229)
- Genentech
- National Heart, Lung, and Blood Institute (N01 HV028183, N01-HV 00242, HHSN268201000034C)
- National Eye Institute (PN2EY018228)
- National Cancer Institute (U54CA119367, P50CA114747, 5R25CA11868107, 5U54 CA143907, U54CA149145, U54-CA-143907, RFA CA 09-011, R25CA118681, R01CA130826, P01CA034233, RFA CA 09-009, P30CA093373, R01 CA120525)
- National Institute of General Medical Sciences (K99GM104148, R00GM104148)
- National Institute of Allergy and Infectious Diseases (U19AI100627, R01AI035304, R01AI073724, HHSN272200700038C, P01AI036535, U19AI057229)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK073928)
- National Center for Research Resources (S10RR027431, S10RR027582)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Physical Sciences › Engineering › Computational Mechanics › Ion-surface interactions and analysis
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- MIBI, breast tumors, secondary ion mass spectrometry, formalin-fixed paraffin-embedded tissue, multiplex immunohistochemistry, antibody labeling, tumor markers
- MeSH terms
- Breast Neoplasms, Female, Humans, Immunohistochemistry, Receptors, Progesterone, Mass Spectrometry, Biomarkers, Tumor, Erb-b2 Receptor Tyrosine Kinases, Estrogen Receptor alpha
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