Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence.
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Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence. / Grupp, Katharina; Kohl, Sebastian; Sirma, Hüseyin; Simon, Ronald; Steurer, Stefan; Becker, Andreas; Adam, Meike; Izbicki, Jakob; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Tsourlakis, Maria Christina.
in: MODERN PATHOL, Jahrgang 26, Nr. 5, 5, 2013, S. 733-742.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence.
AU - Grupp, Katharina
AU - Kohl, Sebastian
AU - Sirma, Hüseyin
AU - Simon, Ronald
AU - Steurer, Stefan
AU - Becker, Andreas
AU - Adam, Meike
AU - Izbicki, Jakob
AU - Sauter, Guido
AU - Minner, Sarah
AU - Schlomm, Thorsten
AU - Tsourlakis, Maria Christina
PY - 2013
Y1 - 2013
N2 - The aim of this study was to determine whether cysteine-rich secretory protein 3 (CRISP3) expression is linked to clinically or molecularly relevant subgroups of prostate cancer. A tissue microarray representing samples from >10,000 prostate cancers from radical prostatectomy specimens with clinical follow-up data were analyzed for CRISP3 expression by immunohistochemistry. CRISP3 expression was also compared with key genomic alterations of prostate cancer. CRISP3 staining was found as weak in 15%, moderate in 8.5%, and strong in 7.2% of prostate cancers, whereas no expression was detected in normal prostate. Strong CRISP3 expression was linked to advanced tumor stage, high Gleason score, and positive surgical margin status (P<0.0001 each). There was a marked accumulation of high CRISP3 expression in PTEN-deleted ERG-positive tumors (P<0.0001). A total of, 21.7% of ERG-positive and PTEN-deleted cancers had strong CRISP3 expression, but only 10.4% of ERG-positive cancers without PTEN deletion (P<0.0001). The rate of high CRISP3 expression was 2.5% in ERG-negative cancers (P=0.0001; vs ERG-positive cancers). Accordingly, CRISP3 overexpression was associated with early prostate-specific antigen recurrence in all tumors (P=0.0013) as well as in ERG-negative (P=0.004) and ERG-positive cancers (P=0.0318). CRISP3 expression did not retain prognostic significance in models also involving PTEN deletions. Strong CRISP3 expression is associated with unfavorable tumor phenotype and early recurrence in prostate cancers. The tight link of strong CRISP3 expression to the ERG fusion-positive prostate cancers with PTEN deletions provides further evidence for the existence of molecularly distinct subgroups of prostate cancers.
AB - The aim of this study was to determine whether cysteine-rich secretory protein 3 (CRISP3) expression is linked to clinically or molecularly relevant subgroups of prostate cancer. A tissue microarray representing samples from >10,000 prostate cancers from radical prostatectomy specimens with clinical follow-up data were analyzed for CRISP3 expression by immunohistochemistry. CRISP3 expression was also compared with key genomic alterations of prostate cancer. CRISP3 staining was found as weak in 15%, moderate in 8.5%, and strong in 7.2% of prostate cancers, whereas no expression was detected in normal prostate. Strong CRISP3 expression was linked to advanced tumor stage, high Gleason score, and positive surgical margin status (P<0.0001 each). There was a marked accumulation of high CRISP3 expression in PTEN-deleted ERG-positive tumors (P<0.0001). A total of, 21.7% of ERG-positive and PTEN-deleted cancers had strong CRISP3 expression, but only 10.4% of ERG-positive cancers without PTEN deletion (P<0.0001). The rate of high CRISP3 expression was 2.5% in ERG-negative cancers (P=0.0001; vs ERG-positive cancers). Accordingly, CRISP3 overexpression was associated with early prostate-specific antigen recurrence in all tumors (P=0.0013) as well as in ERG-negative (P=0.004) and ERG-positive cancers (P=0.0318). CRISP3 expression did not retain prognostic significance in models also involving PTEN deletions. Strong CRISP3 expression is associated with unfavorable tumor phenotype and early recurrence in prostate cancers. The tight link of strong CRISP3 expression to the ERG fusion-positive prostate cancers with PTEN deletions provides further evidence for the existence of molecularly distinct subgroups of prostate cancers.
KW - Adult
KW - Aged
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - Oncogene Proteins, Fusion
KW - PTEN Phosphohydrolase
KW - Prognosis
KW - Prostate-Specific Antigen
KW - Prostatic Neoplasms
KW - Salivary Proteins and Peptides
KW - Seminal Plasma Proteins
KW - Tissue Array Analysis
KW - Tumor Markers, Biological
U2 - 10.1038/modpathol.2012.206
DO - 10.1038/modpathol.2012.206
M3 - SCORING: Journal article
C2 - 23196798
VL - 26
SP - 733
EP - 742
JO - MODERN PATHOL
JF - MODERN PATHOL
SN - 0893-3952
IS - 5
M1 - 5
ER -
