Quantitative Gene Expression Analysis of Androgen Receptor in Benign and Neoplastic Prostate Epithelial Cells May Predict PSA Recurrence
Inger L Rosner*1, Lakshmi Ravindranath*2, Bungo Furusato*2, Yongmei Chen*2, Isabell Sesterhenn*3, David Mcleod1, Shiv Srivastava2, Gyorgy Petrovics2
1Walter Reed Army Medical Center, Washington, DC;2Center for Prostate Disease and Research, Rockville, MD;3Armed Forces Institute of Pathology, Washington, DC
Introduction: Alterations of androgen receptor (AR) are reported in prostate cancer. AR over-expression may have potential to define aggressive clinical behavior in newly diagnosed patients. Quantitative gene expression of AR in laser capture microdissected (LCM) benign and neoplastic epithelial cells from prostatectomy specimens were analyzed.
Methods: 105 hormone naïve patients post radical prostatectomy were studied. Benign and neoplastic prostate epithelial cells were collected with LCM from frozen tissue slides. Expression of AR and GAPDH genes were measured by duplex quantitative real-time RT-PCR in 210 specimens. Fold change of AR expression in tumor (T) versus benign cells (N) was correlated with Gleason score, pathological stage, age, race and PSA recurrence.
Results: Paired t-test compared AR expression normalized to GAPDH in tumor and benign cells. Overall AR expression was 50% lower in tumor versus benign tissue (p=0.0037). Stepwise Logistic Regression with age, race, PSA at diagnosis, pathologic stage, Gleason score, follow up time and AR expression (fold change between T and N) demonstrated increased AR fold change is an independent factor predicting PSA recurrence (p=0.0205). With each 2-fold increase in AR, odds of PSA recurrence increased 36.4%.
Conclusions: Quantitative comparison of AR gene expression in LCM-derived malignant and benign prostate cells may define PSA recurrence. Overall AR expression was lower in the tumor cells. However patients with increased expression of AR in their prostate tumor versus benign cells have an increased risk of PSA recurrence.
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