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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

10/03/2012

Pubmed ID

23026195

Pubmed Central ID

PMC3548055

DOI

10.1016/j.humpath.2012.06.001

Scopus ID

2-s2.0-84873726593   26 Citations

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.

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 MT

Author

Marja T. Nevalainen MD, PhD Assistant Dean, Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
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
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc