Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy. Hum Pathol 2013 Mar;44(3):310-9
Date
10/03/2012Pubmed ID
23026195Pubmed Central ID
PMC3548055DOI
10.1016/j.humpath.2012.06.001Scopus ID
2-s2.0-84873726593 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
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.
Author List
Mirtti T, Leiby BE, Abdulghani J, Aaltonen E, Pavela M, Mamtani A, Alanen K, Egevad L, Granfors T, Josefsson A, Stattin P, Bergh A, Nevalainen MTMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Cell Nucleus
Cohort Studies
Disease Progression
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasm Grading
Neoplasm Recurrence, Local
Predictive Value of Tests
Prognosis
Prospective Studies
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms
STAT5 Transcription Factor
Survival Analysis
Treatment Outcome
Tumor Suppressor Proteins