title: Cytoplasmic accumulation of ELAVL1 is an independent predictor of biochemical recurrence associated with genomic instability in prostate cancer.
abstract: BACKGROUND
  ELAVL1 is an RNA binding protein involved in translation control, which might have a regulatory role in prostate cancer progress.
  
  
  METHODS
  To evaluate its impact and relationship with key genomic alterations, ELAVL1 expression was analyzed by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers.
  
  
  RESULTS
  The analysis revealed a mild to moderate predominantly nuclear immunostaining in normal prostate epithelium and an often higher both cytoplasmic and nuclear expression in cancer cells. Weak, moderate, and strong cytoplasmic ELAVL1 staining was found in 43%, 18%, and 3% of 10,478 interpretable tumors. Strong ELAVL1 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal status, and PSA recurrence (P < 0.0001 each). A combined analysis of the effect of nuclear and cytoplasmic ELAVL1 expression on PSA recurrence revealed that the association with patient outcome was entirely driven by cytoplasmic staining. ELAVL1 positivity was more frequent in cancers harboring TMPRSS2:ERG fusions found by FISH (78%) or showing immunohistochemical ERG expression (74%) than in cancers without ERG rearrangement (63%) or ERG expression (58%, P < 0.0001 each). Strong cytoplasmic ELAVL1 staining was further linked to presence of PTEN, 5q21, 6q15, and 3p13 deletions (P < 0.0001 each), an observation consistent with cytoplasmic ELAVL1 accumulation in case of genomic instability. The prognostic role of ELAVL1 expression was independent of Gleason grade, T stage, N stage, surgical margin status, and preoperative PSA, irrespective of whether preoperative or postoperative variables were used for modeling.
  
  
  CONCLUSIONS
  Our study identifies cytoplasmic accumulation of ELAVL1 as a predictor of adverse clinical behavior of prostate cancer independent of established clinico-pathological parameters.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.|General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Melling
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Berivan
authors.initials: B
authors.lastname: Taskin
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hube-Magg
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Koop
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Grob
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Heinzer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Izbicki
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany.|Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D000067780:ELAV-Like Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D005500:Follow-Up Studies; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human
keywords: ELAVL1; biochemical recurrence; genomic instability; prostate cancer; tissue microarray