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Quantitative Tissue PSA mRNA Expression As A Predictor Of Outcome In Radical Prostatectomy and Alterations In the Androgen Signaling Pathway
Joseph R Sterbis*1, Chun Ling Gao*2, Bungo Furusato*3, Jennifer Cullen*2, Yongmei Chen*2, Lakshmi Ravindranath*2, Isabell A Sesterhenn*3, David G Mcleod1, Shiv Srivastava*2, Gyorgy Petrovics*2
1Walter Reed Army Medical Center, Washington, DC;2Center for Prostate Disease Research, Rockville, MD;3Armed Forces Institute of Pathology, Washington, DC
Introduction: While pre-operative serum PSA is a documented predictor of biochemical outcome following radical prostatectomy, tissue PSA expression has not been similarly investigated. As such, we compared tissue PSA mRNA expression in malignant cells to clinical outcome. We also hypothesized that as an androgen-dependent gene, tissue PSA expression could provide a functional assessment of androgen signaling in prostate cancer.
Methods: Laser-capture microdissection (LCM) identified benign and malignant epithelial cells in 121 patients following radical prostatectomy. Expression of tissue PSA mRNA was determined by quantitative real-time RT-PCR. PSA expression within malignant cells was compared with matched benign cells, serum PSA, Gleason score, pathologic tumor stage and biochemical survival. Regression tree analysis delineated high and low tumor PSA expression groups, which were compared to androgen-dependent (PMEPA1, ERG, DD3) and androgen-independent (LTF, AMACR) gene expression within tumor cells.
Results: Paired T-test demonstrated that malignant cells expressed lower tissue PSA levels than matched benign cells (p=0.0133). Spearman correlation analysis found that PSA serum protein and tissue mRNA levels are not related (p=0.9635). Univariate analysis identified that tissue PSA expression was related to biochemical recurrence (p=0.0130) and pathologic T stage (p=0.0065). Kaplan-Meier analysis confirmed that tissue PSA expression in malignant epithelial cells predicted biochemical recurrence (p=0.0205). While androgen-independent genes demonstrated expression levels independent of tissue PSA, expression of androgen-dependent genes significantly correlated with each other at high tissue PSA.
Conclusions: Independent of serum PSA, decreased neoplastic tissue PSA mRNA expression predicts biochemical recurrence and pathologic T stage, and may represent changes in the androgen-signaling pathway.
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