title: Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence.
abstract: 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.
authors.affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grupp
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kohl
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Sirma
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.forename: Andreas
authors.initials: A
authors.lastname: Becker
authors.forename: Meike
authors.initials: M
authors.lastname: Adam
authors.forename: Jakob
authors.initials: J
authors.lastname: Izbicki
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000096:biosynthesis*; D029589:Seminal Plasma Proteins / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C489926:CRISP3 protein, human; D015514:Oncogene Proteins, Fusion; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins; C515553:TMPRSS2-ERG fusion protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017430:Prostate-Specific Antigen