title: High RNA-binding motif protein 3 expression is an independent prognostic marker in operated prostate cancer and tightly linked to ERG activation and PTEN deletions.
abstract: BACKGROUND
  The RNA-binding motif protein 3 (RBM3) has recently been suspected as a prognostic biomarker in several cancers.
  
  
  METHODS
  RBM3 expression was analysed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancers.
  
  
  RESULTS
  RBM3 expression was more often detectable in malignant compared to benign prostate. RBM3 immunostaining was found in 64% of the interpretable prostate cancers and was considered strong in 25.6%. High RBM3 expression was linked to advanced tumour stage, high Gleason score, positive nodal involvement and positive surgical margin status (p<0.0001 each). There was a remarkable accumulation of strong RBM3 expression in v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) positive prostate cancers and tumours harbouring PTEN deletions (p<0.0001 each). Moreover, RBM3 staining was tightly related to early biochemical recurrence if all tumours or subgroups of ERG negative and ERG positive cancers were analysed (p<0.0001 each). In multivariate analysis, including RBM3 staining, Gleason grade, pT stage, prostate-specific antigen (PSA), surgical margin status, and nodal status, the prognostic impact of RBM3 staining retained statistically significance (p=0.0084).
  
  
  CONCLUSIONS
  Our observations indicate that high RBM3 expression is an independent prognostic marker in prostate cancer. The tight link to ERG activation and PTEN deletions suggest interaction with key molecular pathways in prostate cancer.
authors.affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: k.grupp@uke.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grupp
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: Julia.Wilking@med.uni-giessen.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Wilking
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: k.prien@uke.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Prien
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: c.hube@uke.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hube-Magg
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: h.sirma@uke.de.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Sirma
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: r.simon@uke.de.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: s.steurer@uke.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: budaeus@uke.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Budäus
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: haese@uke.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: izbicki@uke.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Izbicki
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: g.sauter@uke.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: s.minner@uke.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: tschlomm@uke.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: mtsourlakis@uke.de.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D000071230:Transcriptional Regulator ERG
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; C099506:RBM3 protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: ERG; PTEN; Prostate cancer; RBM3; TMA