title: Multiplexed ion beam imaging of human breast tumors.
abstract: 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.
authors.affiliation: 1] Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA. [2] Department of Laboratory Medicine, University of California-San Francisco, San Francisco, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Angelo
authors.affiliation: Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Bendall
authors.affiliation: Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Finck
authors.affiliation: Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Hale
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, California, USA.
authors.forename: Chuck
authors.initials: C
authors.lastname: Hitzman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California-Davis, Health System, Sacramento, California, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California-Davis, Health System, Sacramento, California, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Levenson
authors.affiliation: Department of Pathology, Genentech, South San Francisco, California, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Lowe
authors.affiliation: Department of Pathology, Genentech, South San Francisco, California, USA.
authors.forename: Scot D
authors.initials: SD
authors.lastname: Liu
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Shuchun
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.affiliation: Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA.
authors.forename: Garry P
authors.initials: GP
authors.lastname: Nolan
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human