title: MALDI imaging-based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays.
abstract: OBJECTIVE
  Although most patients with urinary bladder cancer present with noninvasive and low-malignant stages of the disease, about 20% eventually develop life-threatening metastatic tumors. This study was designed to evaluate the potential of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify molecular markers predicting the clinical course of bladder cancer.
  
  
  METHODS
  We employed MALDI-MSI to a bladder cancer tissue microarray including paraffin-embedded tissue samples from 697 patients with clinical follow-up data to search for prognostically relevant associations.
  
  
  RESULTS
  Analysis of our MALDI imaging data revealed 40 signals in the mass spectra (m/z signals) associated with epithelial structures. The presence of numerous m/z signals was statistically related to one or several phenotypical findings including tumor aggressiveness (stage, grade, or nodal status; 30 signals), solid (5 signals) or papillary (3 signals) growth patterns, and increased (6 signals) or decreased (12 signals) cell proliferation, as determined by Ki-67 immunohistochemistry. Two signals were linked with tumor recurrence in noninvasive (pTa category) tumors, of which one was also related to progression from pTa-category to pT1-category disease. The absence of one m/z signal was linked with decreased survival in the subset of 102 muscle-invasive cancers.
  
  
  CONCLUSIONS
  Our data demonstrate the suitability of combining MSI and large-scale tissue microarrays to simultaneously identify and validate clinically useful molecular markers in urinary bladder cancer.
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Julius Magnus
authors.initials: JM
authors.lastname: Singer
authors.affiliation: Department of Urology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Chun
authors.affiliation: Department of Urology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Dahlem
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Burandt
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Phillip
authors.initials: P
authors.lastname: Stahl
authors.affiliation: Department of Pathology, Cantonal Hospital Basel, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Department of Urology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martini Clinic at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Department of Urology, Federal Armed Forces Hospital, Hamburg, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Department of Urology and Pediatric Urology, Medical Center Itzehoe, Itzehoe, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Höppner
authors.affiliation: Department of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maryam
authors.initials: M
authors.lastname: Omidi
authors.affiliation: Department of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Kraus
authors.affiliation: Department of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kwiatkowski
authors.affiliation: Department of Urology, Regio Clinic Wedel, Wedel, Germany.
authors.forename: Ousman
authors.initials: O
authors.lastname: Doh
authors.affiliation: Department of Urology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.affiliation: Department of Urology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Soave
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Department of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Wurlitzer
authors.affiliation: Department of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.affiliation: Department of Pathology at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: s.minner@uke.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
mesh_terms: D000368:Aged; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D046888:Tissue Array Analysis / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology*
keywords: Bladder cancer; MALDI mass spectrometry imaging; TMA; Tissue microarray