Androgen Receptors Are Differentially Expressed in Gleason Patterns of Prostate Cancer and Down-Regulated in Matched Lymph Node Metastases
A Fleischmann, C Rocha, S Schobinger, R Seiler, GN Thalmann. University of Bern, Bern, Switzerland
Background: Androgen receptors (AR) play a central role in prostate cancer. However, heterogeneous distribution with AR negative areas is a constant finding. AR expression profile in the different Gleason patterns (GP) of primary tumors and nodal metastases is unknown and, furthermore, the prognostic potential of AR is controversial. More information about AR distribution is needed to optimize evaluation methods and to better understand the role of AR in development and progression of prostate cancer.
Design: A tissue microarray (TMA) was constructed from 119 hormone-naïve nodal positive, surgically treated prostate cancers containing tissues from all GP present in every primary tumor and the matched metastases. AR expression score was determined immunohistochemically (percentage x staining intensity (1-3)) and correlated with various tumor features and biochemical recurrence-free, disease specific and overall survival.
Results: ARs were up-regulated in primary tumors compared to normal glands and significantly different expressed in the GP (AR scores: GP3=134.8, GP4=157.7, GP5=123.5; p=0.016). A similar expression profile was observed in metastases, however, on significantly lower level (p<0.001). AR expression was not associated with any quantitative (age, prostate cancer volume, number and total size of metastases) or categorical (tumor stage, Gleason score of the primary tumor and metastases) tumor characteristics or with survival.
Conclusions: ARs are differentially expressed in GP what should be considered in prognostic models which include AR. In nodal metastases, ARs are significantly down-regulated suggesting decreased dependence on androgens already under hormone-naïve conditions. The extremely low AR levels in metastatic GP5 might play a role in the predominance of this tissue component in hormone-refractory metastases. AR expression is no prognosticator in nodal positive disease.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 111, Wednesday Afternoon