title: Rapid Detection of Necrosis in Breast Cancer with Desorption Electrospray Ionization Mass Spectrometry.
abstract: Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl]-which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391.25 which is present in small abundance only in viable cancer subregions; and (3) a slight increase in the relative intensity of known breast cancer biomarker ions of m/z 281.25 [FA(18:1)-H]-and 303.23 [FA(20:4)-H]-. Necrosis is accompanied by alterations in the tissue optical depolarization rate, allowing tissue polarimetry to guide DESI-MS analysis for rapid MS profiling or targeted MS imaging. This workflow, in combination with the MS profile of necrosis, may permit rapid characterization of necrotic tumors from tissue slices. Further, necrosis-specific biomarker ions are detected in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the identification workflow by avoiding tissue sectioning and slide preparation.
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tata
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Woolman
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ventura
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bernards
authors.affiliation: STTARR Innovation Center, Princess Margaret Cancer Center, 101 College Street, Toronto, ON M5G 1L7.
authors.forename: Milan
authors.initials: M
authors.lastname: Ganguly
authors.affiliation: Department of Medical Biophysics, University of Toronto,101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Gribble
authors.affiliation: Waters Corporation, 34 Maple Street, Milford, MA 01757, USA.
authors.forename: Bindesh
authors.initials: B
authors.lastname: Shrestha
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Bluemke
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.|Department of Surgery, University of Toronto, 149 College Street, Toronto, ON, M5T-1P5, Canada.|Keenan Research Center for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B-1W8, Canada.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Ginsberg
authors.affiliation: Department of Medical Biophysics, University of Toronto,101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada.|Department of Radiation Oncology, University of Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.|Division of Biophysics and Bioimaging, Ontario Cancer Institute, University Health Network, 610 University Ave, Toronto, ON M5G 2M9, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Vitkin
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
authors.forename: Jinzi
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network, Toronto, ON, M5G-1P5, Canada.|Department of Medical Biophysics, University of Toronto,101 College Street Suite 15-701, Toronto, ON, M5G 1L7, Canada.|Department of Surgery, University of Toronto, 149 College Street, Toronto, ON, M5T-1P5, Canada.|Keenan Research Center for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B-1W8, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Zarrine-Afsar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D005260:Female; D006801:Humans; D007477:Ions; D008055:Lipids / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D051379:Mice; D016513:Mice, SCID; D015233:Models, Statistical; D009336:Necrosis / Q000175:diagnosis*; D025341:Principal Component Analysis; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015415:Biomarkers; D007477:Ions; D008055:Lipids