Significantly Lower Expression Levels of Androgen Receptor (AR) Are Associated with Erythroblastosis Virus E26 Oncogene Related Gene (ERG) Negative (-) Prostate Cancer (PCa)
Jason N Rosenbaum, Sally A Drew, Wei Huang. University of Wisconsin-Madison, Madison
Background: ERG overexpression is correlated with the ERG-TMPRSS2 fusion gene, a mutation known to be present in about 50% of PCa. AR is a known regulator of the ERG-TMPRSS2 fusion gene. Despite knowledge of these relationships, limited data is available on AR expression in PCa in relation to ERG status.
Design: Two prostate tissue microarrays (TMA) were used: progression TMA (pTMA) and outcome TMA (oTMA). The pTMA consists of 384 cores: 43 stage 2 PCa, 30 stage 3 and 4 PCa, 22 metastatic PCa (Mets), 25 high grade intraepithelial neoplasia (HGPIN), 24 benign prostate hyperplasia (BPH) and 48 benign prostate tissues (BPT). The oTMA consists of462 duplicate cores from 48 BPT and 183 PCa (125 without recurrence, 38 with biochemical recurrence and 20 with cancer recurrence either local or distant). Antibodies to e-cadherin (Biocare Medical, 1:100), AR (Biocare Medical, 1:50) and ERG (Epitomics, 1:200) were assayed using a bright field multiplex IHC. TMA sections were stained with the three antibodies and counterstained with hematoxylin. E-cadherin was used to define the epithelial compartment. The TMA slides were scanned with the Vectra™ platform. Biomarker expression analysis was performed with Vectra™ software – both Nuance and inForm™. IBM SPSS Statistics 20 was used for data analysis.
Results: Nuclear AR expression levels were significantly increased in PCa tissue compared to BPT (p<0.01) with highest level in PCa Mets and PCa with cancer recurrence. ERG expression levels were also significantly increased in PCa compared to BPT (p<0.01); however, no clear correlation with either PCa progression or outcome was observed. 49% PCa in pTMA expressed ERG (ERG+) and 53% of PCa in oTMA were ERG+. Comparing ERG+ to ERG- PCa in each subcategory of the two TMAs, AR expression levels in ERG- PCa were significantly lower than those in ERG+ PCa (p<0.01).
Conclusions: Significantly lower AR expression in ERG- PCa suggests a dosage effect of AR in the development of ERG-TMPRSS2 fusion.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 169, Monday Afternoon