title: ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer.
abstract: In prostate cancer genomic rearrangements involving genes encoding ETS transcription factors are commonly present, with androgen-regulated transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogen homologue (ERG) gene fusion occurring in 40-70%. Studies on the predictive value of ERG rearrangement as detected by in-situ hybridization or polymerase chain reaction have resulted in varying outcomes. The objective of this study was to correlate immunohistochemical ERG protein expression with clinico-pathological parameters at radical prostatectomy specimens, and to determine its predictive value for postoperative disease recurrence and progression in a prostate cancer screening cohort. Since androgen receptor is downregulated by ERG in cell lines, we also compared the expression of respective proteins. We selected 481 participants from the European Randomized Study of Screening for Prostate Cancer treated by radical prostatectomy for prostate adenocarcinoma. A tissue microarray was constructed containing representative cores of all prostate cancer specimens as well as 22 xenografts and seven cell lines. Immunohistochemical expression of ERG and androgen receptor was correlated with prostate-specific antigen (PSA), Gleason sum, pT-stage, surgical margins, biochemical recurrence, local recurrence, overall death and disease-specific death. ERG expression was detected in 284 patients (65%). Expression occurred significantly more frequent in patients with PSA ≤10 ng/ml (P=0.024). There was no significant association between ERG and Gleason sum, pT-stage or surgical margin status. PSA (P=0.011), Gleason sum (P=0.003), pT-stage (P=0.001) and surgical margin status (P<0.001) all had independent value for postoperative biochemical recurrence, while positive surgical margin (P=0.021) was the only independent predictor for local recurrence. ERG protein expression did not have prognostic value for the clinical end points in uni- and multivariate analyses. A positive correlation existed between ERG and androgen receptor expression in single tissue cores (P<0.001). In conclusion, immunohistochemical ERG expression has no predictive value for prostate cancer recurrence or progression after radical prostatectomy. Increasing ERG levels are associated with the upregulation of androgen receptor expression in clinical specimens.
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands. A.M.Hoogland@erasmusmc.nl
authors.forename: A Marije
authors.initials: AM
authors.lastname: Hoogland
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
authors.forename: Wytske M
authors.initials: WM
authors.lastname: van Weerden
authors.forename: Jan
authors.initials: J
authors.lastname: Trapman
authors.forename: Theo
authors.initials: T
authors.lastname: van der Kwast
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Mark F
authors.initials: MF
authors.lastname: Wildhagen
authors.forename: Geert Jlh
authors.initials: GJ
authors.lastname: van Leenders
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D011944:Receptors, Androgen / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D011944:Receptors, Androgen; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D017430:Prostate-Specific Antigen