MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays.
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MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays. / Steurer, Stefan; Borkowski, Carina; Odinga, Sinje; Buchholz, Malte; Koop, Christina; Huland, Hartwig; Becker, Michael; Witt, Matthias; Trede, Dennis; Omidi, Maryam; Kraus, Olga; Bahar, Ahmad S.; Seddiqi, A. Shoaib; Singer, Julius M.; Kwiatkowski, Marcel; Trusch, Maria; Simon, Ronald; Wurlitzer, Marcus; Minner, Sarah; Schlomm, Thorsten; Sauter, Guido; Schlüter, Hartmut.
in: INT J CANCER, Jahrgang 133, Nr. 4, 4, 2013, S. 920-928.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays.
AU - Steurer, Stefan
AU - Borkowski, Carina
AU - Odinga, Sinje
AU - Buchholz, Malte
AU - Koop, Christina
AU - Huland, Hartwig
AU - Becker, Michael
AU - Witt, Matthias
AU - Trede, Dennis
AU - Omidi, Maryam
AU - Kraus, Olga
AU - Bahar, Ahmad S.
AU - Seddiqi, A. Shoaib
AU - Singer, Julius M.
AU - Kwiatkowski, Marcel
AU - Trusch, Maria
AU - Simon, Ronald
AU - Wurlitzer, Marcus
AU - Minner, Sarah
AU - Schlomm, Thorsten
AU - Sauter, Guido
AU - Schlüter, Hartmut
N1 - Copyright © 2013 UICC.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Aged
KW - Humans
KW - Male
KW - Middle Aged
KW - Phenotype
KW - Prostatic Neoplasms
KW - Reproducibility of Results
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
KW - Tandem Mass Spectrometry
KW - Tissue Array Analysis
U2 - 10.1002/ijc.28080
DO - 10.1002/ijc.28080
M3 - SCORING: Journal article
C2 - 23381989
VL - 133
SP - 920
EP - 928
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 4
M1 - 4
ER -
