title: MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays.
abstract: To identify molecular features associated with clinico-pathological parameters and TMPRSS2-ERG fusion status in prostate cancer, we employed MALDI mass spectrometric imaging (MSI) to a prostate cancer tissue microarray (TMA) containing formalin-fixed, paraffin-embedded tissues samples from 1,044 patients for which clinical follow-up data were available. MSI analysis revealed 15 distinct mass per charge (m/z)-signals associated to epithelial structures. A comparison of these signals with clinico-pathological features revealed statistical association with favorable tumor phenotype such as low Gleason grade, early pT stage or low Ki67 labeling Index (LI) for four signals (m/z 700, m/z 1,502, m/z 1,199 and m/z 3,577), a link between high Ki67LI for one signal (m/z 1,013) and a relationship with prolonged time to PSA recurrence for one signal (m/z 1,502; p = 0.0145). Multiple signals were associated with the ERG-fusion status of our cancers. Two of 15 epithelium-associated signals including m/z 1,013 and m/z 1,502 were associated with detectable ERG expression and five signals (m/z 644, 678, 1,044, 3,086 and 3,577) were associated with ERG negativity. These observations are in line with substantial molecular differences between fusion-type and non-fusion type prostate cancer. The signals observed in this study may characterize molecules that play a role in the development of TMPRSS2-ERG fusions, or alternatively reflect pathways that are activated as a consequence of ERG-activation. The combination of MSI and large-scale TMAs reflects a powerful approach enabling immediate prioritization of MSI signals based on associations with clinico-pathological and molecular data.
authors: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Stefan
authors: S
authors: Steurer
authors: Carina
authors: C
authors: Borkowski
authors: Sinje
authors: S
authors: Odinga
authors: Malte
authors: M
authors: Buchholz
authors: Christina
authors: C
authors: Koop
authors: Hartwig
authors: H
authors: Huland
authors: Michael
authors: M
authors: Becker
authors: Matthias
authors: M
authors: Witt
authors: Dennis
authors: D
authors: Trede
authors: Maryam
authors: M
authors: Omidi
authors: Olga
authors: O
authors: Kraus
authors: Ahmad S
authors: AS
authors: Bahar
authors: A Shoaib
authors: AS
authors: Seddiqi
authors: Julius M
authors: JM
authors: Singer
authors: Marcel
authors: M
authors: Kwiatkowski
authors: Maria
authors: M
authors: Trusch
authors: Ronald
authors: R
authors: Simon
authors: Marcus
authors: M
authors: Wurlitzer
authors: Sarah
authors: S
authors: Minner
authors: Thorsten
authors: T
authors: Schlomm
authors: Guido
authors: G
authors: Sauter
authors: Hartmut
authors: H
authors: Schlüter
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D046888:Tissue Array Analysis