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Activation of Signal Transducer and Activator of Transcription-5 in Prostate Cancer Predicts Early Recurrence

Authors' Affiliations: ¹ Department of Oncology and ² Biostatistics Unit, Lombardi Comprehensive Cancer Center, Georgetown, University Medical Center, Washington, District of Columbia; ³ Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon; and ⁴ Department of Urology and ⁵ Institute for Pathology, University of Basel, Basel, Switzerland

Requests for reprints: Marja T. Nevalainen, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, NRB W309A, 3970 Reservoir Road Northwest, Washington, DC 20057. Phone: 202-687-2043; Fax: 202-687-7830; E-mail: mtn3{at}georgetown.edu.

Purpose: We have shown previously that the signal transducer and activator of transcription-5 (Stat5) is a critical survival factor in human prostate cancer cells. In addition, we recently showed that Stat5 is activated at a high level, particularly in high-grade human prostate cancers. Here, we investigated whether activation of Stat5 in prostate cancer was linked to clinical outcome with disease recurrence as end point.

Experimental Design: Immunohistochemistry was used to detect active, nuclear Stat5 in 357 paraffin-embedded prostate cancer specimens on a tissue microarray with clinical follow-up data. Stat5 activation status in prostate cancer specimens was analyzed by univariate and multivariate survival analysis to determine whether activation of Stat5 predicts earlier prostate cancer recurrence. Separate sets of statistical analysis were done for all patients regardless of Gleason grade and for patients with prostate cancer of intermediate Gleason grades (3 and 4).

Results and Conclusions: Stat5 activation in prostate cancer was associated with early disease recurrence (P = 0.0399). Importantly, active Stat5 also predicted shorter progression-free survival in intermediate Gleason grade prostate cancers (P = 0.0409). Stat5 activation remained an independent prognostic marker after adjusting for Gleason grade, pT stage, perineural invasion, or seminal vesicle infiltration in all patients (P = 0.0565) and in Gleason grade 3 or 4 patients (P = 0.0582). The results of this work also confirmed our previous finding of association of Stat5 activation with a high histologic grade of prostate cancer (R = 0.11, P = 0.033). In summary, our study shows that active Stat5 distinguished prostate cancer patients whose disease is likely to progress earlier; therefore, active Stat5 may be a useful marker for selection of more individualized treatment. The results of this study need to be validated in a large prospective cohort.

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