PMID- 24584119 OWN - NLM STAT- MEDLINE DCOM- 20140529 LR - 20230701 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 20 IP - 4 DP - 2014 Apr TI - Multiplexed ion beam imaging of human breast tumors. PG - 436-42 LID - 10.1038/nm.3488 [doi] AB - 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. FAU - Angelo, Michael AU - Angelo M AD - 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. FAU - Bendall, Sean C AU - Bendall SC AD - Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA. FAU - Finck, Rachel AU - Finck R AD - Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA. FAU - Hale, Matthew B AU - Hale MB AD - Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA. FAU - Hitzman, Chuck AU - Hitzman C AD - Department of Materials Science and Engineering, Stanford University, Stanford, California, USA. FAU - Borowsky, Alexander D AU - Borowsky AD AD - Department of Pathology and Laboratory Medicine, University of California-Davis, Health System, Sacramento, California, USA. FAU - Levenson, Richard M AU - Levenson RM AD - Department of Pathology and Laboratory Medicine, University of California-Davis, Health System, Sacramento, California, USA. FAU - Lowe, John B AU - Lowe JB AD - Department of Pathology, Genentech, South San Francisco, California, USA. FAU - Liu, Scot D AU - Liu SD AD - Department of Pathology, Genentech, South San Francisco, California, USA. FAU - Zhao, Shuchun AU - Zhao S AD - Department of Pathology, Stanford University, Stanford, California, USA. FAU - Natkunam, Yasodha AU - Natkunam Y AD - Department of Pathology, Stanford University, Stanford, California, USA. FAU - Nolan, Garry P AU - Nolan GP AD - Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA. LA - eng GR - P30 CA093373/CA/NCI NIH HHS/United States GR - 5R25CA11868107/CA/NCI NIH HHS/United States GR - PN2 EY018228/EY/NEI NIH HHS/United States GR - P01 CA034233/CA/NCI NIH HHS/United States GR - N01-HV-00242/HV/NHLBI NIH HHS/United States GR - R01 CA120525/CA/NCI NIH HHS/United States GR - U54CA149145/CA/NCI NIH HHS/United States GR - R21 DK073928/DK/NIDDK NIH HHS/United States GR - 5U54CA143907/CA/NCI NIH HHS/United States GR - P50 CA114747/CA/NCI NIH HHS/United States GR - N01HV28183/HL/NHLBI NIH HHS/United States GR - N01 HV028183/HV/NHLBI NIH HHS/United States GR - R01 CA130826/CA/NCI NIH HHS/United States GR - R01 AI035304/AI/NIAID NIH HHS/United States GR - RFA CA 09-009/CA/NCI NIH HHS/United States GR - P01 CA034233-22A1/CA/NCI NIH HHS/United States GR - U54 CA143907/CA/NCI NIH HHS/United States GR - HHSN268201000034C/HL/NHLBI NIH HHS/United States GR - U19 AI057229/AI/NIAID NIH HHS/United States GR - P01 AI036535/AI/NIAID NIH HHS/United States GR - S10 RR027582/RR/NCRR NIH HHS/United States GR - U19 AI100627/AI/NIAID NIH HHS/United States GR - 1R01CA130826/CA/NCI NIH HHS/United States GR - K99 GM104148/GM/NIGMS NIH HHS/United States GR - R01 AI073724/AI/NIAID NIH HHS/United States GR - S10 RR027431/RR/NCRR NIH HHS/United States GR - U54 CA149145/CA/NCI NIH HHS/United States GR - U54 CA119367/CA/NCI NIH HHS/United States GR - HHSN272200700038C/AI/NIAID NIH HHS/United States GR - S10 OD016318/OD/NIH HHS/United States GR - RFA CA 09-011/CA/NCI NIH HHS/United States GR - R00 GM104148/GM/NIGMS NIH HHS/United States GR - R25 CA118681/CA/NCI NIH HHS/United States GR - PN2EY018228/EY/NEI NIH HHS/United States GR - 1K99 GM104148-01/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20140302 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (Biomarkers, Tumor) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM CIN - Nat Rev Clin Oncol. 2014 May;11(5):240. PMID: 24663125 MH - Biomarkers, Tumor/*metabolism MH - Breast Neoplasms/diagnosis/*metabolism MH - Estrogen Receptor alpha/*metabolism MH - Female MH - Humans MH - Immunohistochemistry/*methods MH - Mass Spectrometry/*methods MH - Receptor, ErbB-2/*metabolism MH - Receptors, Progesterone/*metabolism PMC - PMC4110905 MID - NIHMS601410 EDAT- 2014/03/04 06:00 MHDA- 2014/05/30 06:00 PMCR- 2014/07/25 CRDT- 2014/03/04 06:00 PHST- 2013/05/13 00:00 [received] PHST- 2013/12/17 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2014/05/30 06:00 [medline] PHST- 2014/07/25 00:00 [pmc-release] AID - nm.3488 [pii] AID - 10.1038/nm.3488 [doi] PST - ppublish SO - Nat Med. 2014 Apr;20(4):436-42. doi: 10.1038/nm.3488. Epub 2014 Mar 2.