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.
PURPOSE: We have shown previously that the signal transducer and activator of transcription-5 (Stat5) is a critical survival factor in humanprostate cancer cells. In addition, we recently showed that Stat5 is activated at a high level, particularly in high-grade humanprostate 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 cancerpatients 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.
Authors: M Victoria Recouvreux; J Boyang Wu; Allen C Gao; Svetlana Zonis; Vera Chesnokova; Neil Bhowmick; Leland W Chung; Shlomo Melmed Journal: Endocrinology Date: 2017-07-01 Impact factor: 4.736
Authors: Charles Guo; Guanyu Yang; Kyle Khun; Xiantian Kong; David Levy; Peng Lee; Jonathan Melamed Journal: Am J Transl Res Date: 2009-02-28 Impact factor: 4.060
Authors: Vindhya Udhane; Cristina Maranto; David T Hoang; Lei Gu; Andrew Erickson; Savita Devi; Pooja G Talati; Anjishnu Banerjee; Kenneth A Iczkowski; Kenneth Jacobsohn; William A See; Tuomas Mirtti; Deepak Kilari; Marja T Nevalainen Journal: Mol Cancer Ther Date: 2019-09-23 Impact factor: 6.261
Authors: Ayush Dagvadorj; Shyh-Han Tan; Zhiyong Liao; Luciane R Cavalli; Bassem R Haddad; Marja T Nevalainen Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: Lei Gu; Pooja Talati; Paraskevi Vogiatzi; Ana L Romero-Weaver; Junaid Abdulghani; Zhiyong Liao; Benjamin Leiby; David T Hoang; Tuomas Mirtti; Kalle Alanen; Michael Zinda; Dennis Huszar; Marja T Nevalainen Journal: Mol Cancer Ther Date: 2014-02-27 Impact factor: 6.261
Authors: Priya Koppikar; Vivian Wai Yan Lui; David Man; Sichuan Xi; Raymond Liu Chai; Elizabeth Nelson; Allison B J Tobey; Jennifer Rubin Grandis Journal: Clin Cancer Res Date: 2008-12-01 Impact factor: 12.531