title: Loss of PTEN expression in ERG-negative prostate cancer predicts secondary therapies and leads to shorter disease-specific survival time after radical prostatectomy.
abstract: The clinical course of prostate cancer is highly variable. Current prognostic variables, stage, and Gleason score have limitations in assessing treatment regimens for individual patients, especially in the intermediate-risk group of Gleason score 7. ERG:TMPRSS2 fusion and loss of PTEN are some of the most common genetic alterations in prostate cancer. Immunohistochemistry of PTEN and ERG has generated interest as a promising method for more precise outcome prediction but requires further validation in population-based cohorts. We studied the predictive value of ERG and PTEN expression by immunohistochemistry in two large radical prostatectomy cohorts comprising 815 patients with extensive follow-up information. Clinical end points were initiation of secondary therapy, overall survival, and disease-specific survival. Predictions of clinical outcomes were also assessed according to androgen receptor (AR) activity. PTEN loss, especially in ERG-negative cancers, predicted initiation of secondary treatments and shortened disease-specific survival time, as well as stratifying Gleason score 7 patients into different prognostic groups with regard to secondary treatments and disease-specific survival. High AR immunoreactivity in ERG-negative cancers with PTEN loss predicted worse disease-specific survival. We also observed that in Gleason score 7 ERG-negative cases with PTEN loss and high AR expression have significantly shorter disease-specific survival time compared with ERG-positive cases. Our conclusion is that loss of PTEN is a strong determining factor for shorter disease-specific survival time and initiation of secondary therapies after radical prostatectomy. The predictive value of PTEN immunoreactivity is further accentuated in ERG-negative cancers with high AR expression. Negative PTEN expression, accompanied by ERG status, can be used to stratify patients with Gleason score 7 into different survival groups. Assessment of PTEN and ERG status could provide an additional tool for initial diagnostics when determining the prognosis and subsequent follow-up regimen for patients treated by radical prostatectomy.
authors: Department of Urology, Meilahti Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Kanerva
authors: K
authors: Lahdensuo
authors: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors: Andrew
authors: A
authors: Erickson
authors: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Irena
authors: I
authors: Saarinen
authors: Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Heikki
authors: H
authors: Seikkula
authors: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors: Johan
authors: J
authors: Lundin
authors: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
authors: Mikael
authors: M
authors: Lundin
authors: Department of Pathology, HUSLAB and Medicum, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Stig
authors: S
authors: Nordling
authors: United Medix Laboratories, Pathology, Helsinki, Finland.
authors: Anna
authors: A
authors: Bützow
authors: Department of Urology, Meilahti Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Hanna
authors: H
authors: Vasarainen
authors: Department of Urology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Peter J
authors: PJ
authors: Boström
authors: Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.
authors: Pekka
authors: P
authors: Taimen
authors: Department of Urology, Meilahti Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Antti
authors: A
authors: Rannikko
authors: Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.|Department of Pathology, HUSLAB and Medicum, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors: Tuomas
authors: T
authors: Mirtti
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000071230:Transcriptional Regulator ERG / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human