Decrease in the Tyrosine Phosphorylated Stromal Androgen Receptor Level Is Associated with High Grade Prostate Cancer
S Jain, MQ Yu, JH Wang, N Aladhamy, D Zhang, M Zhang, G Daniels, XT Kong, S Logan, ZY Guo, Y Qiu, J Melamed, P Lee. New York Univeristy SOM, New York, NY; Mount Sinai SOM, New York, NY; University of Maryland SOM, Baltimore, MD
Background: Hormone-deprivation is of the mainstream therapy for advanced prostate cancer, however, invariably, it leads to hormone-refractory prostate cancer (HRPC). Serine and tyrosine phosphorylation of androgen receptor (AR) by growth factors or receptor tyrosine kinases may be one of the mechanisms involved in the development of HRPC by increasing the AR transcriptional activity under androgen deprivation. In this study, we delineated the role of tryrosine phosphorylated stromal AR in the progression of prostate cancer.
Design: Immunohistochemistry was performed using antibody against tyrosine phosphorylated AR (pARY534) to characterize its expression pattern in the stromal cells on a tissue microarray (TMA)(n=110) of 36 hormone resistant prostate cancer, 34 hormone-naïve, 20 after neo-adjuvant treatment. Control tissue included10 non-neoplastic tissue samples after neo adjuvant radical and 10 non-neoplastic tissue with no preceding treatment. The levels of pARY534 expression were scored by analysis of 50 stromal cells and expressed as percentage of positive cells. Non-parametric Wilcoxon and Poisson regression tests were performed for statistical significance in correlation with various clinocopathological parameters.
Results: pARY534 expression in cancer stromal cells showed a decrease (63%) as compared to stromal cells in normal prostate (73%)(p=0.02). The extent of decrease in pARY534 levels correlated with increase in grade as follows:median of 74% for Gleason score ≤7 and 62% for Gleason >8 (p=0.0001). Stromal pARY534 expression in hormone refractory cancer decreased from 72% in stromal cells in non-neoplastic prostate to 61% in stromal cells of prostate cancer (p=0.019) with no difference between hormone naïve and hormone refractory cancer. In neo-adjuvant treated group, there is an increase of stromal pARY534 in non-neoplastic prostate to 83%. Similarly, there is a 13% decrease (p=0.056) in the group with cancer after neo-adjuvant therapy. The lower levels of pARY534 expression were associated with decreased overall survival, 61% for deceased and 73% for alive patients (p value <0.0001) by Poisson regression test.
Conclusions: Decrease in the stromal tyrosine phosphorylated androgen receptor level is associated with high grade prostate cancer.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 115, Wednesday Afternoon