title: High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence.
abstract: Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the prognostic impact of PDGFR-β and its ligands (PDGF-B and PDGF-D) in a multicenter prostatectomy cohort of 535 Norwegian patients. Using tissue microarrays and immunohistochemistry, the expression of ligands PDGF-B and PDGF-D and their corresponding receptor, PDGFR-β, was assessed in neoplastic tissue and tumor-associated stroma. PDGFR-β was expressed in benign and tumor associated stroma, but not in epithelium. High stromal expression of PDGFR-β was independently associated with clinical relapse (HR = 2.17, p = 0.010) and biochemical failure (HR = 1.58, p = 0.002). This large study highlights the prognostic importance of PDGFR-β expression, implicating its involvement in prostate cancer progression even in early stage disease. Hence, analyses of PDGFR-β may help distinguish which patients will benefit from radical treatment, and since PDGFR-β is associated with relapse and shorter survival, it mandates a focus as a therapeutic target.
authors.affiliation: Dept Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Dept Urology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Nordby
authors.affiliation: Dept Clinical Pathology, University Hospital of North Norway, Tromso, Norway.|Dept Medical Biology, The Arctic University of Norway, Tromso, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.affiliation: Dept Medical Biology, The Arctic University of Norway, Tromso, Norway.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Rakaee
authors.affiliation: Dept Medical Biology, The Arctic University of Norway, Tromso, Norway.
authors.forename: Nora
authors.initials: N
authors.lastname: Ness
authors.affiliation: Dept Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Dept Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.affiliation: Dept Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Dept Urology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Hiten R H
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Dept Clinical Pathology, University Hospital of North Norway, Tromso, Norway.|Dept Medical Biology, The Arctic University of Norway, Tromso, Norway.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Dept Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Dept Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.affiliation: Dept Clinical Medicine, The Arctic University of Norway, Tromso, Norway.|Dept Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D009928:Organ Specificity; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011468:Prostatectomy / Q000401:mortality; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta