title: Variations in the Abundance of Lipid Biomarker Ions in Mass Spectrometry Images Correlate to Tissue Density.
abstract: While mass spectrometry (MS) imaging is widely used to investigate the molecular composition of ex vivo slices of cancerous tumors, little is known about how variations in the cellular properties of cancer tissue can influence cancer biomarker ion images. To better understand the basis for variations in the abundances of cancer biomarker ions seen in MS images of relatively homogeneous ex vivo tumor samples, sections of snap frozen human breast cancer murine xenografts were subjected to desorption electrospray ionization mass spectrometry (DESI-MS) imaging. Serial sections were then stained with hematoxylin and eosin (H&E) and subjected to detailed morphometric cellular analysis, using a commercial digital pathology platform augmented with custom-tailored image analysis algorithms developed in-house. Gross morphological heterogeneities due to stroma, vasculature, and noncancer cells were mapped in the tumor and found to not correlate with the areas of suppressed cancer biomarker abundance. Instead, the ion abundances of major breast cancer biomarkers were found to correlate with the cytoplasmic area of cancer cells that comprised the tumor tissue. Therefore, detailed cellular analyses can be used to rationalize subtle heterogeneities in ion abundance in MS images, not explained by the presence of gross morphological heterogeneities such as stroma.
authors.affiliation: STTARR Innovation Centre, Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Jade
authors.initials: J
authors.lastname: Bilkey
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network , Toronto, Ontario M5G-1P5, Canada.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tata
authors.affiliation: STTARR Innovation Centre, Princess Margaret Cancer Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: McKee
authors.affiliation: ThoMSon Mass Spectrometry Laboratory, Institute of Chemistry, University of Campinas , Campinas, SP Brazil.
authors.forename: Andreia M
authors.initials: AM
authors.lastname: Porcari
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network , Toronto, Ontario 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, Ontario 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, Ontario M5G-1P5, Canada.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ventura
authors.affiliation: ThoMSon Mass Spectrometry Laboratory, Institute of Chemistry, University of Campinas , Campinas, SP Brazil.
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.affiliation: Techna Institute for the Advancement of Technology for Health, University Health Network , Toronto, Ontario M5G-1P5, Canada.|Department of Medical Biophysics, University of Toronto ,101 College Street Suite 15-701, Toronto, Ontario M5G 1L7, Canada.|Department of Surgery, University of Toronto , 149 College Street, Toronto, Ontario M5T-1P5, Canada.|Keenan Research Centre for Biomedical Science, Li Ka-Shing Knowledge Institute, St. Michael's Hospital , 30 Bond Street, Toronto, Ontario M5B-1W8, Canada.
authors.forename: Arash
authors.identifier: 0000-0002-8013-6893
authors.initials: A
authors.lastname: Zarrine-Afsar
mesh_terms: D000465:Algorithms; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007477:Ions / Q000737:chemistry; D008055:Lipids / Q000032:analysis*; D051379:Mice; D016513:Mice, SCID; D021241:Spectrometry, Mass, Electrospray Ionization; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D007477:Ions; D008055:Lipids