title: Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy.
abstract: There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. Most PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death. In preclinical PCa models, Stat5a/b promotes PCa growth and progression. Stat5a/b is critical for PCa cell viability in vitro and for tumor growth in vivo and promotes metastatic dissemination of cancer in nude mice. Here, we analyzed the predictive value of high nuclear Stat5a/b protein levels in 2 cohorts of PCas: Material I (n = 562) PCas treated by radical prostatectomy (RP), and Material II (n = 106) PCas treated by deferred palliative therapy. In intermediate GS PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariable analysis; P < .0001, multivariable analysis; HR = 1.82, P = .017) and early PCa-specific death (univariable analysis; P = .028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariable (P < .0001) and multivariable (HR = 1.61; P = .012) analysis in the entire cohort of patients treated by RP regardless of the GS. Patients treated by deferred palliative therapy, elevated nuclear Stat5a/b expression was associated with early PCa-specific death by univariable Cox regression analysis (HR = 1.59; 95% CI = [1.04, 2.44]; P = .034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after RP for intermediate GS PCas.
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki and HUSLAB, Helsinki 00014, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mirtti
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Leiby
authors.forename: Junaid
authors.initials: J
authors.lastname: Abdulghani
authors.forename: Elina
authors.initials: E
authors.lastname: Aaltonen
authors.forename: Miia
authors.initials: M
authors.lastname: Pavela
authors.forename: Anita
authors.initials: A
authors.lastname: Mamtani
authors.forename: Kalle
authors.initials: K
authors.lastname: Alanen
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.forename: Andreas
authors.initials: A
authors.lastname: Josefsson
authors.forename: Par
authors.initials: P
authors.lastname: Stattin
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
authors.forename: Marja T
authors.initials: MT
authors.lastname: Nevalainen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus; D015331:Cohort Studies; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D025521:Tumor Suppressor Proteins; D017430:Prostate-Specific Antigen