title: MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.
abstract: For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hinsch
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Buchholz
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Odinga
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Borkowski
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Koop
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Dept. of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wurlitzer
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Krech
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Jacobsen
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: E-C
authors.initials: EC
authors.lastname: Burandt
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Stahl
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: R
authors.identifier: 0000-0003-0158-4258
authors.initials: R
authors.lastname: Simon
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Dept. of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schlüter
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005557:Formaldehyde; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D009362:Neoplasm Metastasis; D016612:Paraffin Embedding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D046888:Tissue Array Analysis; D016707:Tissue Fixation; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D005557:Formaldehyde
keywords: MALDI; colon cancer; tissue microarray