title: Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry.
abstract: Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies.
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2].
authors.forename: Charlotte
authors.initials: C
authors.lastname: Giesen
authors.affiliation: 1] Department of Chemistry, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland. [2] Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland. [3].
authors.forename: Hao A O
authors.initials: HA
authors.lastname: Wang
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Systems Biology Ph.D. Program, Life Science Zürich Graduate School, ETH Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Schapiro
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Molecular Life Science Ph.D. Program, Life Science Zürich Graduate School, ETH Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: Nevena
authors.initials: N
authors.lastname: Zivanovic
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jacobs
authors.affiliation: Department of Chemistry, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
authors.forename: Bodo
authors.initials: B
authors.lastname: Hattendorf
authors.affiliation: Department of Computer Science, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schüffler
authors.affiliation: Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grolimund
authors.affiliation: Department of Computer Science, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Buhmann
authors.affiliation: Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Brandt
authors.affiliation: Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.affiliation: Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.affiliation: Department of Chemistry, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
authors.forename: Detlef
authors.initials: D
authors.lastname: Günther
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bodenmiller
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D019044:Image Cytometry / Q000379:methods*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins